* 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]]]].