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Frank Moses (Willis), a former black-ops CIA agent who is now in RED (Retired, Extremely Dangerous) status, lives alone in Cleveland. Lonely, Frank creates opportunities to talk to Sarah Ross (Parker), a worker at the General Services Administration’s pension office in Kansas City, by tearing up his pension checks and calling to say they have not arrived.
One night, an assassination squad raids Frank’s house and attempts to kill him but he easily eliminates them all. Knowing they will have tapped his phone, he believes Sarah will be targeted. In Kansas City Sarah refuses to go with him so he kidnaps her. Meanwhile, CIA agent William Cooper (Urban) is assigned by his corrupt boss Cynthia Wilkes (Pidgeon) to hunt down and kill Frank.
To find out who is targeting him, Frank tracks down some of his old associates for help. He goes to New Orleans, Louisiana, and visits his CIA mentor Joe Matheson (Freeman), who tells him the same hit squad murdered a New York Times reporter. An agent posing as a police officer tries to abduct Sarah but Frank returns in time. Cooper chases them but Frank tricks the police into arresting Cooper and escapes with Sarah. The two head to New York City and find clues left by the reporter which lead them to a hit list.