Edward Wilson (Matt Damon) is partly based upon the founder of the C.I.A.'s counterintelligence operations, James Jesus Angleton.

Robert De Niro had been working on this film for ten years as his "pet project".

Joe Pesci's first movie in eight years.

When Wilson and Hayes are standing in the lobby of the under-construction C.I.A. Headquarters talking about the quote on the wall, Edwards asks what it means. Hayes replies "That's classified". The reply was appropriate, considering this would come to be known as the Wall of Honor, where undercover C.I.A. Agents, killed while on a mission would be honored only by a single star carved into the wall. There would be no names mentioned, because their work is classified.

Joe Pesci appeared in one scene as a Mafia boss (Joseph Palmi) who, it is implied in the film, 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.

Edward Wilson's (Matt Damon's) name is close to that of real-life C.I.A. Agent Edwin Wilson, who was involved in one of the most controversial episodes in the agency's history. An ex-Marine and Korean War veteran, the real Ed Wilson left the C.I.A. and was subsequently jailed for supplying arms and ex-Green Beret mercenaries as trainers to Libyan terrorist training camps. Wilson always claimed he was acting on C.I.A. orders and gathering intelligence on their behalf, later being exonerated and freed when released documents proved the C.I.A. had lied about severing all links with Wilson before the events occurred. A former C.I.A. Officer, David Adler, was the lawyer who got Wilson's conviction overturned.

The character Yuri Modin is loosely based on Soviet defector Anatoliy Golitsyn.

Matt Damon specifically noted that this film, along with Syriana (2005), was a risky and hard-hitting project that he was able to do in the wake of massive success of The Bourne Identity (2002) and The Bourne Supremacy (2004)).

General Bill Sullivan (Robert De Niro) is partly based on General William "Wild Bill" Donovan. Donovan was head of the Office of Strategic Services (OSS) during World War II.

Phillip Allen (William Hurt) is partly based on Allen Dulles, O.S.S. operative, and later C.I.A. Director during the Bay of Pigs invasion. Contrary to popular belief, President John F. Kennedy was fascinated with the world of espionage and unconventional warfare, granting the U.S. Special Forces their trademark Green Berets, while his enthusiasm for the James Bond novels helped to popularize them. However, during the C.I.A.'s Bay of Pigs operation he refused to allow overt military support for the mission, and severely limited the number of air strikes allowed to be flown by the C.I.A.'s own aircraft, for fear of revealing the U.S. Government's role. Both decisions are widely considered to have doomed the entire enterprise to failure from the start. Ironically, Allen Dulles was appointed to the Warren Commission investigating the assassination of President Kennedy, Dulles' former boss. Kennedy had fired Allen Dulles as head of the C.I.A.

Robert De Niro had a deal with Leonardo DiCaprio, who was interested in playing the film's protagonist Edward Wilson. De Niro planned to shoot the movie in the fall of 2004, but DiCaprio couldn't do it then, because he was making The Departed (2006) for Martin Scorsese. The role ultimately went to Matt Damon, who played DiCaprio's antagonist in The Departed (2006). Both movies were nominated for Oscars.

Richard Hayes (Lee Pace) shares some similarities, including a similar name, to Allen Dulles' (C.I.A. Director from 1953-1961) eventual successor Richard Helms (C.I.A. Director from 1966-1973).

Matt Damon studied Gene Hackman's performance in The Conversation (1974) in preparation for this role.

Dr. Ibanez (Marcos Cohen) bears some similarities, and is probably a reference to, Jacobo Arbenz (President of Guatemala from 1951-1954).

Margaret's (Angelina Jolie's) nickname is "Clover", which was Allen Dulles' wife's real name

Eddie Redmayne plays the son of Damon and Jolie despite being only eleven and six years younger, respectively.

Eric Roth penned the screenplay in 1994 for Francis Ford Coppola and Columbia Pictures. Coppola left the project because, he said, he could not relate to the characters, finding them "unemotional", (although he retained a credit as co-Executive Producer).

Two references to "Cardinal" are made in the movie, once in the beginning when the comment that "Cardinal is interested" is made by Ray Brocco and once at the end when Edward Wilson says that "it's a cardinal rule to be generous in a democracy". "Cardinal" was the code name of a high level American spy in the Soviet Union in Tom Clancy's novel The Cardinal of the Kremlin.

The film cast includes seven Oscar winners: Robert De Niro, Matt Damon, Angelina Jolie, William Hurt, Joe Pesci, Timothy Hutton, and Eddie Redmayne; and one Oscar nominee: Alec Baldwin

First cinema film of Eddie Redmayne.

The name "Bay of Pigs" is a direct translation of "Bahia de Cochinos".

James Horner was signed to compose the score, but quit due to creative differences with Director Robert De Niro. Marcelo Zarvos replaced him soon afterward, and was assisted by Bruce Fowler.

The violinist providing the solo soundtrack near the end of the movie was Lindsay Deutsch, from Los Angeles.

The filming location of the Deer Island Club was Great Camp Sagamore on Raquette Lake in the Adirondacks. Sagamore was built by prominent designer and developer William West Durant, and is a notable example of the Gilded Age Adirondack Great Camp architecture. It was the summer retreat of the Vanderbilt family. The Sagamore interior proved to be too small to accommodate the entire film production crew, so a replica was constructed in New York City.

Leonardo DiCaprio was originally cast as the younger Edward Wilson, but dropped out.

Wayne Wang was set to direct, but management changes at Columbia ended Wang's involvement, and Philip Kaufman was the next person set to direct, but he eventually left the project. When it moved to MGM, John Frankenheimer signed on to make the movie and wanted Robert De Niro to star. Unfortunately, Frankenheimer died in 2002, and at the same time, De Niro was developing his own spy story.

Jude Law was considered for the role of Edward Wilson.

One of two films released on 2006 starring both Alec Baldwin and Matt Damon. The other film was The Departed (2006).

Eddie Redmayne and Matt Damon, who play father and son here, were in competition with one another for Best Actor at the 2015 Academy Awards. Both lost out to Leonardo DiCaprio.

Philippe Vonlanthen was requested by Robert De Niro to be seen for the role of the "Cambridge Club Butler" after their initial meeting in Brooklyn, New York. The part ultimately went to an older actor, Robert Ian Mackenzie.

Stephanie Linus was considered for a role in the film.

John Frankenheimer was briefly attached to direct.

Edward Wilson's house in Washington, D.C. resembles the Spring Valley neighborhood in the northwest section of the city.

Robert De Niro and Amy Wright appeared in The Deer Hunter (1978).

Ray (John Turturro) tells Edward (Matt Damon), "There's a stranger in our house." Tammy Blanchard (Laura) appeared in Stranger in the House (2015).

Amy Wright and William Hurt appeared in The Accidental Tourist (1988).

William Hurt, Billy Crudup, and Josh Casaubon appeared in Too Big to Fail (2011).

Matt Damon and William Hurt appeared in Syriana (2005).

Matt Damon and John Turturro appeared in Rounders (1998)

Robert De Niro and John Turturro appeared in Raging Bull (1980) and What Just Happened (2008).

Eddie Redmayne and William Hurt appeared in The Yellow Handkerchief (2008).

Robert De Niro and Billy Crudup starred together 10 years prior in Sleepers (1996).

Archy Cummings (Billy Crudup) was partly based on real-life British traitor Kim Philby, who attended Cambridge University, rose through the ranks of British Intelligence, and subsequently was discovered to be a Soviet spy. He later fled to Moscow, where he lived out the rest of his life. The movie reflects this, having Wilson speaking by phone to Cummings, who is in the Soviet Union.

Dr. Fredericks (Michael Gambon) was partly inspired by Alan Turing, a British mathematician who helped to crack the German "Enigma" code during World War II, and who is considered one of the founders of modern computer science. In 1952, Turing was expelled from the British Secret Service after being prosecuted for his homosexual affairs. In 1954, he died after eating a cyanide-laced apple, but it is unknown if he was murdered or committed suicide.

Throughout the film, every main antagonist tells Edward Wilson his weakness.

They give the "real" Valentin liquid LSD, which causes him to go crazy, ultimately restating that he is, indeed, Valentin Mironov, before committing suicide by jumping through the glass window. This is a reference to a real event wherein Frank Olson, a U.S. Army scientist, died in a similar way in 1953, allegedly as a result of his unwitting participation in LSD experiments, which were part of the C.I.A.'s "MKULTRA" program.

As previously mentioned there are two references to Cardinal; one in the beginning and one in the end. Both instances involve the exchange of a dollar. In the end, Edward's line regarding a "cardinal rule" could imply that Ulysses' bodyguard is in fact "Cardinal", a member of the K.G.B. and spy for the West.

Throughout the movie, several references to feet or shoes are made: The General's feet and eventual amputation; being "bootmakers to kings", tying of Edward's shoes as code.