* In the book, the end of the chapter where Neville finds the dog. After spending a month trying to get the last living creature on Earth other than himself to allow Neville to pet him, it finally looks like he will have a companion. It'll be easier just to read it yourself:
--> [[spoiler: "You'll be all better soon," he whispered. "Real soon."]]
--> [[spoiler: The dog looked up at him with its dulled, sick eyes and then its tongue faltered out and licked roughly and moistly across the palm of Neville's hand.]]
--> [[spoiler: Something broke in Neville's throat. He sat there silently while tears ran slowly down his cheeks.]]
--> [[spoiler: In a week, the dog was dead.]]
* [[spoiler: Virginia returning from her grave. And then few chapters later Neville tearfully tells Ruth how it feels to [[StakingTheLovedOne stake your own wife]] and how much effort it takes to convince yourself she's no longer the woman you love]].
* During the flashbacks, an infected mother can be seen begging for her daughter to be taken to safety in the middle of the chaos to leave Manhattan.
* When Sam [[spoiler:gets infected whilst saving Neville's life and he's forced to MercyKill her. Not only did he lose his only companion of the last three years, but also one of the last remaining links to his family at the same time]].
* In the movie, the aforementioned [[spoiler: Shoot The Dog moment]], and the moment Dr. Neville begs [[spoiler: the mannequin]] to say hello to him, since he had promised Sam he would try for it. Though some found the latter Narmy.
* Who didn't tear up during the climax of the film, especially when he tries negotiating with the infected trying to break down his door moments after he finds the cure, desperately hoping to get through to them and prove that the last three years and all his suffering haven't been in vain.
--> '''Neville:''' LET ME SAVE YOU!!!!
** For that matter, the original climax. [[spoiler:While there's ultimately a happy ending for everyone, the male Darkseeker's grief, fury, and sheer, broken ''relief'' are all extremely palpable. Throw in Neville's WhatHaveIDone moment and it's powerful stuff all around.]]
* The "Look Daddy, a butterfly" line right before [[spoiler: Dr. Neville's demise and the death itself]].
* The ''true'' ending of that movie, the one [[spoiler:where Neville realizes that the vampires are the good guys and ''he'' is the monster of ''their'' legends, hence the title]]. But [[ExecutiveMeddling the studio forced the filmmakers to make a more generic kill-em-all ending]].
** The real ending also kind of makes the scene with [[spoiler:Sam all the more tragic, when you realize [[FridgeHorror Sam could have been saved]]]].
* The tie in comics, some of which were also released as animated shorts. [[spoiler: Don’t expect a lot of happy endings.]]
** '’Death is a Gift’’: Shown from the perspective of a sole survivor in Hong Kong [[spoiler: Not only do they end up [[DrivenToSuicide committing suicide,]] [[DespairEventHorizon either out of despair]], [[BetterToDieThanBeKilled not wanting to be hunted down by the dark seekers]] or both. A suicide note the deceased carried on them [[CruelTwistEnding reveals they were one of the few humans Immune to the Krippin virus]].]]
** '’Shelter’’: Written from the perspective of a young Indian girl (Pritam) who disobeys her father’s wishes to stow away in a shelter, and sneaks out to the infected streets of New Delhi to see her Boyfriend one more time. [[spoiler: Pritam's family ends up locking her out of the shelter, out of fear of being infected. Pritam succumbs to the Krippin Virus, which in turn mutates her into a dark seeker. [[DownerEnding Pritam reunites with her boyfriend, who also mutated in to a dark seeker, and they both murder and consume the rest of the girl's family]].]]
** ''Isolation’’: Written form the Perspective of an infamous Super Max inmate left to die alone in prison. [[spoiler: He escapes, only to be hunted down and backed to a corner by the dark seekers, the last minutes reveal he was a [[KnightTemplar Moral Extremist]] who engaged in acts of Domestic Terrorism. [[BolivianArmyEnding The last frame is of him preparing his last stand as the dark seekers close in on him]].]] Despite the mans crimes, it would have probably been more humane to just put a bullet in the guys head over just letting him dehydrate and starve to death alone.
*** What’s worse is that in the end, [[spoiler: after pumping his shotgun, only one gunshot is heard, hinting that he actually took his own life rather than be mauled to death by the Dark Seekers.]]