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When it comes to TV shows that took the world by storm and became a hit, it is impossible not to highlight Grey’s Anatomy. This production, created by Shonda Rhimes, premiered on ABC back in March 2005 and has now been on the air for 19 seasons so far, making it the longest scripted primetime show carried by the network. And that’s not all: earlier this year, the TV series was renewed for an additional season (via Deadline).

This medical drama show follows the day-to-day lives of the doctors and employees of Seattle Grace Hospital, focusing particularly on Meredith Grey’s storyline. Originally, the cast featured Ellen Pompeo, Sandra Oh, Katherine Heigl, Justin Chambers, T. R. Knight, Chandra Wilson, James Pickens Jr., Isaiah Washington, and Patrick Dempsey, although over the course of the seasons it underwent many changes, with some actors leaving the show and others joining in. As of today, Pickens and Wilson are the only two original cast members who are still main actors, as Pompeo left the show in its 19th season.

Throughout the many, many episodes of this acclaimed TV show, the audience engages with stories of all kinds, involving not only doctors, but also patients. And, as is often the case with medical drama shows, Grey’s Anatomy certainly has its fair share of heartbreaking moments that made fans weep. Here are 20 of the saddest episodes of this popular TV show that will definitely make you cry.

Into You Like a Train (Season 2, Episode 6)
Grey’s Anatomy
ABC
Some of the patients who cross the doors of Seattle Grace Hospital manage to stick in the audience’s heart forever, even though their stories are limited to a single episode. That is exactly the case with Tom and Bonnie, a man and a woman who, following a train accident, are pierced by a metal pole that leaves their bodies connected. As if their injuries aren’t serious enough, their doctors have a tough decision ahead of them: only one of them is likely to survive once the metal pole is removed.

Didn’t We Almost Have It All? (Season 3, Episode 25)
Preston Burke and Cristina Yang in Grey’s Anatomy
ABC
“Didn’t We Almost Have It All?” is the episode that wrapped up Grey’s Anatomy Season 3, and a pretty sad one for everyone who loves Cristina Yang, the character played by Sandra Oh. After many ups and downs in her relationship with Dr. Burke, the two are getting married in a ceremony witnessed by their family and friends.

This entire situation makes Cristina incredibly nervous, so she tries to keep herself busy in the hours leading up to the event. Still, she gladly puts her fears aside as she prepares to marry the man she considers to be the love of her life. Burke, however, gets cold feet at the last minute, so he ends up walking out on his fiancée moments before saying “I do.”

During the 10th season of the show, Kelly McCreary joined the Grey’s Anatomy cast to play Maggie Pierce, the biological daughter of Ellis Grey and Richard Webber and Meredith’s half-sister. As the episodes went on, fans grew to love this quirky character to pieces, which is why “Be Still, My Soul” was such an emotional episode.

In it, the hospital doctors attempt to find a cure for Maggie’s adoptive mother’s tumor, but things look complicated and Maggie is not ready to come to grips with the fact that her mother won’t be around for much longer.

Death and All His Friends (Season 6, Episode 24)
Grey’s Anatomy, episode “Death and All His Friends”

Grey’s Anatomy Season 6’s finale was one of the most nail-biting finales in the entire show. In this double episode, the hospital enters lockdown after a shooter comes in seeking revenge for the death of his wife, a former patient.

One of the man’s victims is Derek, who gets shot in the chest. When Cristina and Jackson take him to the OR to save his life, they are confronted by the shooter, who is determined to do whatever it takes to verify that Derek is gone. The hospital team manages to trick him into thinking that he is dead, but the fake news reaches Meredith, who miscarries her unborn child out of shock.

Good Mourning (Season 6, Episode 1)
Grey’s Anatomy, episode “Good Mourning”
ABC
The show’s fifth season finale leaves fans on the edge of their seats after Izzie and George, two of the most beloved characters on the show, are on the verge of dying. The sixth season of Grey’s Anatomy kicks off with “Good Mourning,” an episode in which it is finally revealed that Izzie made it through, but George did not. Over the course of this heartbreaking episode, we witness how George’s friends and family try to cope with grief in the best way they can.

Sarah Drew plays Dr. April Kepner, who was initially quite irritating, but ended up winning over the audience. That is why “Cold as Ice” made many people cry, as April is involved in an accident that almost gets her killed, which upsets all her coworkers and, particularly, Jackson, her daughter’s father. When he thinks everything is lost, Jackson asks God not to take April away, offering his faith in return, a promise he eventually keeps after she makes a miraculous recovery.

14Leave a Light On (Season 16, Episode 16)
Grey’s Anatomy, episode “Leave a Light On”

“Leave a Light On” is a very moving Grey’s Anatomy episode for many, as it marked the farewell of Alex Karev, portrayed by Justin Chambers. Alex was one of the few characters who was there from the very beginning of the show, and although he was quite obnoxious at first, he grew a lot over the seasons and became one of the audience’s favorites.

When the actor exited the show in Season 16 looking for new opportunities, so did his character: in the show, he met up with Izzie, the love of his life, and after discovering that she had had children out of the embryos they had frozen when they were together, he decided to stay with her and give their family a chance. This, of course, meant abandoning his life in Seattle and all the people who love him, including his wife Jo.

Since Alex doesn’t feel empowered enough to break the news upfront, he vanishes without notice and, eventually, sends letters to each of them explaining what happened. The conclusion of Chambers’ character’s storyline disappointed many fans, but even so this episode still brought a few tears to people’s eyes.

13Drowning on Dry Land (Season 3, Episode 16)
Grey’s Anatomy, episode “Drowning on Dry Land”
ABC
Meredith Grey came close to dying on many, many occasions throughout the show. One of them happened during its third season, when she fell into icy water while she was helping the victims of a ferryboat accident. Given such a chaotic situation with casualties and injured people all around, no one notices that Meredith is drowning, except for a little girl who can’t speak, so she spends a long time struggling to stay afloat, until she eventually gives up.

In “Drowning on Dry Land”, the audience witnesses the tremendous efforts of all the doctors who, despite their hopelessness, do their utmost to keep Meredith alive.

12It’s the End of the World (Season 2, Episode 16)
“It’s the End of the World” is another episode in which Meredith comes close to dying. This time, the hospital is jeopardized after a man shows up in the ER with a bomb inside his body that hasn’t exploded yet because a paramedic is keeping it in place by using her hand. But when this young woman, portrayed by Christina Ricci, panics and pulls her hand out, Meredith steps in, putting herself in an extreme situation.

11The Perfect Storm (Season 9, Episode 24)
Grey’s Anatomy, episode “The Perfect Storm”
The show’s ninth season wrapped up with one extremely stressful episode in which a massive storm hit Seattle, leaving Grey Sloan Memorial Hospital with no electricity and in chaos. As if dealing with the power outage and all the patients wasn’t enough, Meredith goes into labor in the midst of the blackout.

Of course, something goes wrong with the C-section and, after delivering her son, she finds herself fighting for her life in the OR. To make matters worse, the final scenes of the episode reveal that, while trying to fix the emergency generators, Dr. Richard Webber is shocked and left unconscious on the floor.

10The Sound of Silence (Season 12, Episode 9)
Grey’s Anatomy, episode “The Sound of Silence”
ABC
Taking care of the patients at the hospital can be quite a complicated task, and at times, it can even lead to serious health problems. That’s what happens to Meredith in “The Sound of Silence,” the ninth episode of the show’s 12th season, when she is brutally attacked by a patient who suddenly regains consciousness.

As a result of the incident, she suffers several fractures and must undergo a jaw operation that prevents her from speaking for several weeks, coping on her own with the psychological consequences of the attack.

9Fear (of the Unknown) (Season 10, Episode 24)
Grey’s Anatomy, episode “Fear (Of The Unknown)”

From the very beginning of the show, Meredith Grey and Cristina Yang have been the best of friends and kept each other company like no other. And although their bond remained the same over the years, as of the end of the show’s 10th season, fans had to come to terms with the reality that Cristina would no longer be on-screen following Oh’s departure from the cast.

In “Fear (of the Unknown),” Cristina leaves Seattle for a new challenge: to assume as Director of Cardiothoracic Surgery at the Klausman Institute for Medical Research. And while all her friends are happy for her new opportunity, her exit leaves many of them heartbroken.

8Going, Going, Gone (Season 9, Episode 1)
Grey’s Anatomy, episode “Going, Going, Gone”
ABC
The show’s eighth season wrapped up with one of the saddest episodes in its history: the one that involved a plane crash that killed several members of the staff. Grey’s Anatomy’s ninth season, for its part, kicks off with the events following the accident, revealing how all the characters are coping with the aftermath of the crash.

However, the saddest part of this episode centers around Dr. Mark Sloan, who survived the accident, but was left with after-effects that ultimately led to his devastating death.

7All I Could Do Was Cry (Season 11, Episode 11)
Grey’s Anatomy, episode “All I Could Do Was Cry”
ABC
“All I Could Do Was Cry” brought Dr. April Kepner face to face with her own crisis of faith upon receiving the news that her unborn child suffers from a terminal illness. After so many years of being a strong believer, she starts to question God’s existence, or at the very least, his sense of justice.

Throughout this episode, the audience follows April and Jackson through their labor induction process, witnessing the few minutes they are able to spend with their baby, whom they name Samuel Norbert Avery.

6Helplessly Hoping (Season 17, Episode 7)
Grey’s Anatomy, episode “Helplessly Hoping”
ABC
“Helplessly Hoping” is yet another sad episode in the show, as it marks Giacomo Gianniotti’s exit, and with him, the departure of his character, who passes away after being stabbed while confronting a child trafficker. In this particular case, the character’s death was not due to the actor’s departure from the cast: when showrunner Krista Vernoff approached Gianniotti with that storyline for DeLuca, he simply couldn’t say no.

5Fight the Power (Season 17, Episode 5)
Grey’s Anatomy, episode “Fight The Power”

The COVID-19 pandemic and the efforts of doctors during this difficult time was one of the major topics of the show’s 17th season. In the episode “Fight the Power,” we see our beloved doctors attempting to save the lives of their patients, even though they don’t quite know how to do it.

However, there is one particular story that draws the audience’s attention: the one involving Dr. Bailey and her mother, a woman who suffers from Alzheimer’s disease and reaches the hospital with a very advanced case of COVID that ends up leading to her death.

4Losing My Religion (Season 2, Episode 27)
Grey’s Anatomy, episode “Losing My Religion”
ABC
“Losing My Religion” is the episode that wraps up the show’s second season and puts an end to the ongoing story between Izzie Stevens and Denny Duquette. Dr. Stevens risked her career to get Denny a heart transplant, but before she could even deal with the consequences of her actions, her lover has a stroke and passes away, leaving her grief-stricken and unable to move on.

3Now or Never (Season 5, Episode 24)
Grey’s Anatomy, episode “Now Or Never”

When it comes to deaths that left fans devastated, it is impossible not to think of George O’Malley, the first major character to die on the show. In “Now or Never,” the doctors are busy treating Izzie, who underwent surgery to cure her cancer, but they also devote some time to care for a stranger who shows up at the ER severely disfigured after jumping in front of a bus to save a woman.

Eventually, we learn that this man is none other than George, one of the hospital’s most beloved doctors, who unfortunately fails to recover from the consequences of his heroic deed.

2Flight (Season 8, Episode 24)
Grey’s Anatomy, episode “Flight”
ABC
If it hasn’t become clear by now, the season finales of Grey’s Anatomy are known for being particularly tense and emotional, and the final episode of the show’s eighth season was no exception. In it, some of the doctors fly to assist in a surgery at a hospital in Boise, but the plane crashes and leaves them all stranded in a forest with severe injuries.

Thus, Meredith and the rest of the team must stay alive until someone comes to their rescue, but sadly, Lexie Grey passes away in one of the most heart-breaking scenes of the entire show.

1How to Save a Life (Season 11, Episode 21)
Grey’s Anatomy, episode “How To Save A Life”

Since the very first episode of Grey’s Anatomy, the audience followed Meredith and Derek’s love story. This couple that started out as a casual hook-up grew into a beautiful family, and over time, became one of television’s favorite couples ever. However, they did not get their happily ever after, as after being involved in a terrible car accident, Derek is left with major injuries and passes away in the hospital, while in the company of the love of his life.