* Cristina crying in Owen's arms over the death of her father.
* Izzie breaking down crying when [[spoiler:Denny dies]].
* Izzie's famous "What about me?" speech to Denny when [[spoiler: she tells him of her plan to cut his LVAD wire so that he will qualify for the heart transplant]].
** The season five finale: Meredith realizing that John Doe is [[spoiler: George]], Izzie flatlining in Alex's arms and then meeting [[spoiler: George]] in the elevator, dressed in his army uniform.
* [[FromBadToWorse Dark Was The Night]], an unrelentingly bleak episode in which everything that can go wrong does.
* This happens in the season eight finale, [[WhamEpisode "Flight".]]
* If you have grown up around or known alcoholics, Lexie's rant to Meredith in 4.08 is heartbreaking.
-->''Lexie:'' Everyday is my mothers birthday. My mother was born in March. He lied. He's a liar. And I'm glad. Really, I'm glad that you found him charming. I'm sure he was delightful. He's a blast after five drinks, not so much after nine though; he gets a little weepy and mean. He's a drunk, Meredith. He probably came in and told you how wonderful you are. How sad he is he doesn't get to spend more time with you. You know, yesterday he told me I was his favorite daughter. The day before, I was an ungrateful bitch. The week before, he wrote me a check for $20,000 because he said I deserved everything life had to offer, because he was so proud of me, a lifetime's worth of proud. So thank you for letting me know that I need to keep a better eye on him. Thanks.
* In season 9 there's an episode of a liver transplant patient. The patient, who is gay, had been waiting for a liver for so long that he was still married to a woman when he got sick. Him and his husband are excited, talking wanting to spend 30 additional years together to make up for lost time, since it took him such a long time to come out. The patient does finally get the liver, but his body rejects it, and him and his husband only have a few days left together. An intern starts crying and even Cristina looks sad.
* Another episode has two single parents, both with newborns in the ICU, bond over the shared experience and become each others' close friend/confidant and support system. The woman has been waiting for a heart transplant for her daughter for a long time, while the man's son seems to be doing better. Then the boy starts to get a lot worse, just as the hospital has a heart available, and he bypasses the girl, who is at the top of the list. This causes a rift between the two - the mother is appalled by this revelation and immediately distances herself from the other parent who is overcome with guilt. At the end, they are still upset but the woman tries to be happy for the guy instead of being angry.
* [[spoiler: The death of Dr. Thomas]], which sends Cristina right back to Seattle Grace.
* The aftermath of season 8's plane crash: Every scene from first few episodes of season 9 of Callie and Arizona, the days leading up to [[spoiler: Mark's death and him waking up just to end up knowing he will be dying soon]], the Cristina and Owen scenes, etc.
** The actual plane crash episode when [[spoiler: Lexie tells Mark she loves him as she is dying.]]
* Richard leaves his ailing wife's side and attends Bailey's wedding. Why? [[spoiler: ''Because Adele died.'' The last shot of the episode is an ImagineSpot of her and Richard dancing at their own wedding.]]
* Season 8 has an episode in which Morgan, one of Alex's interns, gives birth prematurely. The baby has a ton of health problems and the father spends the whole time complaining about how he's missing work (he worked at a different hospital) and not wanting to be there for his sick child. Morgan gives the father an out, and he doesn't hesitate to walk out on his girlfriend and newborn son by the end of the episode. Morgan starts to lean on [[JerkWithAHeartOfGold Alex]] for support but ends up falling for him, which causes him to keep his distance. Then the baby eventually dies a few episodes later.
* "Damage Case" (season 2). A family is hit in a car accident by an intern from another hospital (played by JohnCho). At first it seems that the family is fine and that they're mostly just for laughs while the real medical issues are with Cho's character. However, this assumption is turned on its head when [[spoiler: one family member's catastrophic injuries are revealed while Cho's character was merely tired]]. The tears really get jerked when [[spoiler: JohnCho apologizes to the father for killing his pregnant daughter]].