Angelina Jolie admitted in an interview with Vogue Magazine that the only reason she agreed to do this movie was because she knew it would be a "quick shoot" in Venice, Italy.
On the strength of his previous movie, The Lives of Others (2006), director Florian Henckel von Donnersmarck was granted a large amount of control in casting decisions and the screenplay for his big-budget Hollywood debut. However, when shooting began, his famous lead actors took control, and in the end, he said had very little creative input. When asked later why he chose to do the film, he stated that he simply could not resist making a movie with two of the world's most charming actors in the world's most beautiful location.
Sam Worthington replaced Tom Cruise, who was originally going to play Frank Tupelo. Johnny Depp then replaced Worthington, when the latter withdrew from the film over "creative differences".
The extras feature titled "Action In Venice" commentary states that actors and crew who had to enter the Venetian water were put on antibiotics for weeks beforehand, as the water was deemed so polluted.