Leonard Shelby has short term memory loss resulting from an injury he sustained which was associated with the murder of his wife. He remembers his life prior to the incident, such as being an insurance claims investigator. He has learned to cope with his memory loss through dealing with a man named Sammy Jankis, a person he investigated professionally who also had short term memory issues. Some of these coping mechanism are to have a system of where to place things, talk to people face-to-face if possible rather than on the telephone as to be able to gauge their true intention, take Polaroids and write copious notes, the most important of those which he tattoos on his body so that they become permanent. Leonard's current mission is to find and kill his wife's murderer, who he believes is a man named John G., a name which is tattooed on his body. Over the course of a day, Leonard is assisted in this mission by a few people seemingly independent of each other, including a man named Teddy and a woman named Natalie. However, each time he meets them, he has no idea who they are, why they are helping him and if indeed they are working toward the same goal as him.