Denzel Washington was actually waterboarded during the filming of some of the torture scene, though only for a few seconds per take.
Thanks to a clause in the contract giving Denzel Washington director approval, Espinosa wasn't fired, despite artistic differences between him and the producers. Denzel said that he wanted Espinosa to direct, and that's that, so the producers let Espinosa finish the movie.
During the filming of the 'escape from the boot of the car' scene, performed with actual full-speed, unprotected driving by Reynolds, as he and Denzel wrestle for control of the car, Ryan's head smashed into Denzel, giving him a lump over his right eye. They reset for a new take, filming from the other side so as to hide the injury, and it happened again, giving D.W. matching forehead lumps. This necessitated a halt in production for a couple of days, during which, according to Reynolds, Denzel "resembled an old-fashioned Christmas ornament!"
Safe House is the most financially successful film ever by a Swedish director.
In an early draft of the screenplay, Matt Weston's ability to catch up to Tobin Frost was explained thusly: during his time at the CIA's academy for new agents in training, "The Farm", Frost's file was assigned to Weston as his case study. Weston had memorized Frost's history and used this data to explain to the CIA leaders where Frost would go once he was on the run. The scenes where Weston tracks down Frost in the South African township were kept for the final draft, but altered so Weston used ad hoc research skills to locate his charge.