Frank Horrigan (Clint Eastwood) is a tough, veteran Secret Service agent who has been plagued by feeling s of guilt and failure since the assassination of John F. Kennedy. As the agent on duty that fatal day, Horrigan feels that he should have reacted more quickly and taken the bullet for the President.

Thirty years later, the current President of the United States is entering a re-election campaign, and following a number of death threats, Horrigan has been called in to assist in what should be a routine research operation.

However, when he discovers that a professional assassin and master of disguise (John Malkovich) has been tracking the President, the assignment turns into a deadly game of cat and mouse. Leary uses his knowledge of the events in 1963 to mentally torture Horrigan in the ensuing psychological duel – a duel that will eventually put Horrigan 'In the Line of Fire'...