According to Richard Donner, Mel Gibson improvised the opening scenes in which his character expounds his conspiracy theories to a succession of passengers.
The secret CIA MKUltra program that forms a key factor of the plot for the movie is real and well documented. It ran from 1953 to 1973 when the then-director of the CIA ordered all the files destroyed. A cache of 20,000 documents was somehow preserved and subsequently released by a freedom of information request in 1977.
According to an interview with director Richard Donner on the DVD of Payback: Straight Up Director's Cut (2006) he met screenwriter Brian Helgeland when he was driving at the Warner Brothers gate, and saw Brian holding a sign that said "Will write for work, for money". Richard got out of the car and asked him about the sign, Brian replied that he was a screenwriter, and was looking for work. Donner had decided to give Helgeland a chance, which led to the two of them working on this movie. Helgeland also worked with Donner on Assassins (1995).
The doctor, who lets Julia Roberts into the restricted area to see Mel Gibson handcuffed to the bed, is Gibson's younger brother Donal Gibson. He also comes in to help Gibson when he is having a heart attack.
In the movie, several times an earthquake is referenced that took place on a southern coast, with a magnitude of 7.3 during a Presidential visit. A 7.3 earthquake did indeed happen in the Northwest part of Turkey in 1999, just to be followed by a Presidential visit.
Richard Donner: Jerry's cab passenger in the opening credits. He is the passenger with the grey hair mullet and glasses.