Point blank in the head a man shoots another. In flashbacks, each one earlier in time than what we've just seen, the two men's past unfolds. Leonard, as a result of a blow to the head during an assault on his wife, has no short-term memory. He's looking for his wife's killer, compensating for his disability by taking Polaroids, annotating them, and tattooing important facts on his body. We meet the loquacious Teddy and the seductive Natalie (a barmaid who promises to help), and we glimpse Leonard's wife through memories from before the assault. Leonard also talks about Sammy Jankis, a man he knew with a similar condition. Has Leonard found the killer? What's going on?