15 of the Most Gut-Wrenching Grey's Anatomy Moments Ever

When Addison arrives at Seattle Grace, Derek is forced to make a choice: rescue his marriage or maintain his new flame with Meredith. After days of trying to play it cool, Meredith cracks and pleads with Derek: "Pick me. Choose me. Love me."

In a desperate attempt to move Denny up the transplant list for a new heart, Izzie cuts his LVAD wire. His condition worsens, but he recovers and asks her to marry him. After donning a dress for the prom party for Dr. Webber's niece, Izzie returns to find Denny dead. The other interns discover Izzie curled up next to Denny in his bed, sobbing.

The usually cool-headed Derek finally reaches his limit as he discovers Meredith half-dead of hypothermia in ice-cold water while the other doctors treat the victims of a ferryboat accident. After she flatlines, he blames her mother, Ellis, for ruining her daughter's spirit.

After weeks of painful wedding preparation that is so not Cristina, Burke realizes that he's forced her to be someone she isn't, and lets her go at the altar. Sobbing and gasping for air, she asks Meredith to rip her dress off and cries, "He's gone. I'm free."

After discovering his love for trauma medicine by working with Owen Hunt, George enlists in the army. The rest of the doctors stage an intervention to talk him out of it, but they're unsuccessful. Not long after he leaves, a severely disfigured man is admitted to Seattle Grace after jumping in front of a bus to save a stranger. He writes "007" on Meredith's hand with his finger, and she realizes it's George—but he doesn't survive surgery. We've never gotten over it, honestly.

Callie's father shows up at Seattle Grace after she tells him that she is in a relationship with Arizona. He brings a pastor to talk her out of it but she yells, "You can't pray away the gay."

A disgruntled relative of a patient Derek was unable to save enters Seattle Grace and begins shooting indiscriminately—but his ultimate goal is Derek. He eventually shoots Derek on the iconic walkway and Cristina must restrain Meredith as she watches him fall.

After the shooting and high-pressure surgery she performs to save Derek's life, Cristina quits the surgical program. Derek takes Cristina fishing as a last-ditch effort to help her come to terms with her emotions. Finally, while taking a picture with her catch of the day, she breaks down and releases a flood of tears. Fish will do that to you.

Teddy marries Henry, a patient with failing kidneys, to help him get access to health insurance, but their relationship becomes more than transactional. When he begins vomiting blood, she takes him to hospital, but is called away to a long and complicated surgery. Henry passes away; Owen orders Cristina not to tell Teddy as she enters the OR to work alongside her. Only when the surgery is over does she learn the truth.

Several of the doctors at Seattle Grace are involved in a plane crash on the way to a surgery in Boise. Lexie is crushed under the wing of the plane and Mark consoles her during her last breaths, finally confessing the life he wishes he could have had with her.

After the plane crash, Cristina is catatonic and unresponsive, apart from occasionally lashing out violently. Owen is washing her gently in the tub when she finally reveals the horrors she experienced in the woods while waiting to be rescued: listening to the wolves devour Lexie, drinking her own pee, and not eating for three days. It's heartbreaking.

Richard and Adele look like they'll actually get their happily ever after when he agrees to take a step back from work—but after she has several unexplained falls, they discover that Adele has Alzheimer's. Eventually, she forgets Richard completely, even when he sings "My Funny Valentine," the song they danced to at their wedding.

Cristina leaves Grey Sloan Memorial for a job in Zurich. The besties' goodbye is brief and awkward, so Cristina turns her cab around to reunite with Meredith for a poignant final dance party. She says goodbye to Meredith as only someone's "person" could: "He [Derek] is not the sun. You are." Cue endless crying.

After walking in on an intoxicated Jo with Andrew, Alex assumes they had sex and beats him to a pulp, allowing his old violent tendencies to take over—sparking a lawsuit and suspension from surgery.

In a gut-wrenching plot twist, Derek dies in a car crash while narrating the mistakes that doctors are making. But in reality, he is unable to speak because he has sustained brain trauma. Meredith makes the decision to switch off his life support—and a cornerstone relationship of the series is ended.