The 20 Most Heartbreaking Grey’s Anatomy Episodes

Izzie Stevens (Katherine Heigl) and her patient Denny Duquette (Jeffrey Dean Morgan) were going to get married and probably live a long and happy life together, until their future crumbled before them. Izzie went as far as almost getting fired for breaking hospital protocol in order to save Denny from his heart issues, but in the end he died anyway.

Cristina Yang was such a cold, hardened badass on the surface that it made her few moments of weakness even more staggering. In this episode, she's left at the altar by Burke, which is sad enough on its own. But then, right before she begs Meredith to rip her out of the wedding dress that seems to be suffocating her, she says, "I'm free." Her subsequent sobs seem to both mourn the loss of Burke and celebrate the relief of being unburdened from a marriage she might not have wanted too much to begin with.

For half of this episode, Grey Sloan’s doctors attempt to figure out the identity of a mystery patient who's been hit by a bus. Heartbreakingly, viewers and surgeons came to the realization at the same time: it’s George O'Malley (T.R. Knight). He'd just left his job to join the army, but on his way out of the hospital, he suffered irreparable injuries while saving a woman from an oncoming bus. He died a hero, but his death was no less devastating.

The hospital shooter episode of Grey's Anatomy is one of the show’s most jarring. It was unexpectedly bloody, and it showed no mercy — taking the lives of several doctors and forever changing those who survived. In one of the most distressing moments, Cristina operated on Derek Shepherd (Patrick Dempsey) at gunpoint while a traumatized Meredith experienced a miscarriage.

The arc of Richard Webber's (James Pickens Jr.) first wife, Adele (Loretta Devine), was one of the series' most painful and realistic, but it's often overlooked in favor of flashier, more shocking storylines. Still, watching Adele beg Richard not to dismiss her as a burden as she battles Alzheimer’s will always stand out as one the show’s most emotional moments. Actor Loretta Devine won an Emmy for her portrayal.

Teddy (Kim Raver) and Henry (Scott Foley) are one of the most underrated couples on all of Grey's. The two initially only got married so that Teddy could help Henry cover his expensive medical treatments, but later fell in love. They were perfectly happy together until his health took a turn for the worse. Even more twisted, Cristina — Teddy’s prodigy — was tricked into performing the surgery that ultimately resulted in Henry’s death. The news that he’d died was then hidden from Teddy so she wouldn't mess up her own surgery, and she didn't find out what happened until almost the end of the next episode.

The Season 8 finale included one of the biggest Grey's Anatomy catastrophes. A plane carrying Meredith, Derek, Lexie (Chyler Leigh), Mark (Eric Dane), and Arizona (Jessica Capshaw) crashed in the middle of the wilderness, resulting in several injuries — some of them fatal. In perhaps the most heartbreaking moment, Mark stayed by Lexie's side and held her hand as she took her final breaths. To reassure her in those final moments, he told her that he loved her and that she would make it through. If only.

In the episode following the plane crash, it seemed like Mark was going to be OK. But then he abruptly lapsed into a coma and never woke up again. His death particularly affected Callie (Sara Ramirez), with whom he shared a child, and Derek, his best friend. The emotional impact was made worse by the happy flashbacks of Mark peppered throughout the episode.

After Adele's death, Richard still showed up to Miranda Bailey's (Chandra Wilson) wedding, because he knew he had to be there to support his mentee. But even amidst the merriment, Richard couldn't help but shed a tear over losing his wife and having no one there to comfort him in his mourning.

April and Jackson knew that something troubling was happening with April's pregnancy a few episodes before she actually gave birth, but that didn't soften the blow of this harrowing episode. After learning that their child had a medical issue and wouldn’t be able to survive outside of the womb, the two made the difficult decision to have the baby and cherish it for the very little time they would have. Jackson then tried to embrace God in a last-ditch effort to help April grieve as they said goodbye to their son Samuel. This loss later became a driving force in April and Jackson's divorce.

Even if you're not a rabid Derek fan, this episode likely tore you to pieces. His death was an avoidable one — if his doctors had given him the correct treatment, he would have survived. His inner monologue as he realized he was dying would bring anyone to tears, and that's before watching Meredith find out that her husband was gone.

In this episode, Maggie (Kelly McCreary) struggles to let go of her mother, who’s dying of cancer. In her final moments, Maggie paints her mother’s nails. She continues in silence even after realizing that she’s gone.

When April's faith was shaken by a particularly bad surgery outcome, a new patient, Rabbi Eli, restored her beliefs. He helped April see that faith isn't just believing when things are good, but believing that the bad will pass and that God has a plan. Watching April return to her religious roots — which were central to her character on the show — while comforting Eli in his final moments was hard to watch. Her character may have gotten what she needed, but it wasn't a happy, celebratory scene.

After getting into a bad accident, April nearly died. Jackson sat beside her bed for every moment of her recovery, crying and promising to share April's sense of faith in God if she got to live. She ended up pulling through, which made the fact that she and Jackson still weren't together that much more upsetting. It took several more seasons for them to finally get back together.

In this episode, Jo Wilson (Camilla Luddington) learned that she was the product of rape. Her story was set against that of Abby Redding, a rape survivor who came into the hospital after being brutally attacked. The episode showed, in excruciating detail, what rape survivors experience after being assaulted. On her way to the operating room, Abby was afraid to see any men. So women doctors lined the hall to support her after surgery.

Because Maggie was adopted, she doesn't know much about her biological family. In this episode, Maggie meets her cousin Sabi for the first time when she comes into the hospital to get treatment for a cardiac tumor. The two bond quickly, which makes her death — on Maggie's operating table, no less — all the more agonizing.

Grey’s Anatomy star Justin Chambers left the show in 2020, and this episode revealed what became of his character Alex Karev. The actor had already unknowingly filmed his final scene, so the other characters simply got letters from Karev explaining why he had skipped town. It was an abrupt and unsatisfying exit for a beloved character made even sadder by the damage it caused to his wife Jo and best friend Meredith.

Grey's Anatomy’s 17th season portrayed the coronavirus pandemic while the real world was still in the midst of the worst of it. Watching Miranda sit beside her dying mother wrapped in protective gear felt even more bleak knowing that so many families had done the same for their loved ones.

After going several seasons without a major character death, Grey's Anatomy delivered a gut punch with Andrew DeLuca's (Giacomo Gianniotti) sudden demise. He was stabbed while pursuing a child sex trafficker, and his wounds were fatal. This episode came after his death and featured a heartbreaking socially distant memorial service at which DeLuca's friends recounted what an amazing doctor and person he was.

After contracting coronavirus, Meredith spent much of Season 17 unconscious, traveling in her mind to a kind of purgatory beach where she had conversations with her dead loved ones — including Derek. It seemed like Meredith was ready to give up and join him, but Meredith's daughter Zola (Aniela Gumbs) sat by her bedside begging her mother to wake up. Zola's voice seemed to help Meredith come back to the real world, and while it was joyous to see her pull through, it was sad to see her once again have to leave Derek.