Leonard Shelby was a regular happily-married man with a good job until his house was broken into and his wife was murdered. In a scuffle with the attackers that night, Leonard hit his head and lost his capacity for short-term memory. The last memory he has is watching his wife die. After the police investigators show themselves to be incapable of delivering justice to the killers, Leonard dedicated his life to tracking down his wife's killers on his own and killing them, with the feelings of rage always fresh in his mind.

Part of Leonard's problem is that he has no real friend to help him through his troubles. In his book The Myth of Neurosis, Garth Woods describes the role of the "concerened friend" as one who "helps elucidate problems so that the individual can increase his self-respect by solving them." Instead of these concerened friends, Leonard knows only people who are seeking to take advantage of his memory condition. According to Woods, in a healthy relationship each friend "uses the other as a semi-permanent shoulder to cry on in return for continual testimonials as to their wisdom, stability, and sensitivity." The closest peopel that Leonard has to friends are Teddy and Natalie, who both use him as a thug to accomplish their own goals without leaving Leonard any way of knowing what he has become.

The ambiguity of Leonard's actions are greatly increased by his memory condition. Because of his condition, one instance of giving in to temptation towards evil has the potential to lead him down a long road of suffering for himself and those around him. Leonard does give in to this temptation, and it does ultimately lead to the death of Teddy and a future which holds little promise for Leonard. However, because his most sinful actions stem from a single action which, while stil evil in itself, would not be considered a mortal sin.