The real Robert Baer (the author of "See No Evil", on which this screenplay is based) plays "CIA Security Officer #2".
The scene at the front doorway of the Sloan Whiting law firm, which is immediately adjacent to the U.S. Capitol, is actually the real law firm Jones Day located at 51 Louisiana Avenue, NW
Greta Scacchi played Bob Barnes' wife and Robby Barnes' mother in a role cut from the final release.
Due to the weight he gained for the film, George Clooney suffered a spinal injury during a stunt that caused him severe migraine headaches (which prevented him from doing publicity for Ocean's Twelve), and had him bedridden for a month. This injury was eventually corrected with surgery, and Clooney has since called his weight gain "pretty stupid".
In the original draft of the script, the character of Bob Barnes was originally named Bob Baer, after Robert Baer's father.
When Bob (George Clooney) meets with Hossein Hashimi, Hashimi compliments Bob for his fine Arabic, yet in fact, Bob only speaks the first word - of his supposed all-Arabic line - in Arabic, then mumbles the rest in non-Arabic.
Harrison Ford was the original choice to play Bob Barnes, but turned it down. He later told Empire magazine that is one of the few movie career decisions that he has regretted.
In the days leading to the Oscar nominations, the Academy announced that the screenplay for this film was considered original, not adapted. Since it had been strongly advertised as the latter, many believed that it would not be nominated. However, it did manage to receive a screenplay nod, losing to Crash.
George Clooney gained 35 pounds on a pasta-heavy diet to play CIA operative Robert Barnes. The actor also shaved his hairline for the right look.
Stephen Gaghan had wanted Christian Bale to play Bryan Woodman, but he had to turn the part down due to his commitment to The New World.
The scene where George Clooney is going to meet with his son where it says Princeton University is actually the area in front of Sellinger Hall at Loyola College in Maryland.
Michelle Monaghan originally had a more substantial role in the film, but when screening audiences reacted negatively to the long running time, her sub-plot was removed, similar to what happened to the actress on the film Constantine.
Syriana is a term used by Washington think-tanks to describe a hypothetical re-shaping of the Middle East.
SPOILER: In the Hossein Hashimi assassination scene, an actor with a remarkable physical appearance to former CIA director George Tenet can be seen milling in the background in the CIA operations room.