Edward Wilson (Matt Damon) is partly based upon the founder of the C.I.A.'s counterintelligence operations, James Jesus Angleton.
Joe Pesci appeared in one scene as a Mafia boss (Joseph Palmi) who, it is implied in this movie, is a fictionalized version of Sam Giancana (in one scene, it is mentioned that Fidel Castro has seized "three of (Palmi's) casinos and thrown him out of (Cuba)". In fact, Castro did "nationalize" several Giancana-controlled casinos). The C.I.A. recruited Giancana for several assassination attempts on Castro. His character could also be mirrored after Santo Trafficante, who was temporarily detained in Cuba after his own casinos were nationalized. Trafficante was a mafia boss in Florida (where the meeting in the movie takes place), while Giancana was a member of the Chicago Outfit.
Matt Damon studied Gene Hackman's performance in The Conversation (1974) in preparation for this role.
General Bill Sullivan (Robert De Niro) is partly based on General William "Wild Bill" Donovan. Donovan was head of the Office of Strategic Services (O.S.S.) during World War II.