With the influx of cast and crew, the existing population of Castel del Monte - 129 people - was more than doubled. When a crew member needed emergency dental work, he had to go to a nearby town as the answering machine of Castel del Monte's dentist declared that he was "unavailable, due to his appearance in a Hollywood film."
Violante Placido is the daughter of Simonetta Stefanelli who, as Apollonia, stunned Michael Corleone, in O Poderoso Chefão (1972) some 40 years before this film's similar American-hiding-in-Italy was stunned by her daughter.
The reason why George Clooney's character chews gum a lot in the film is that the character simply doesn't have a lot of dialogue and Anton Corbijn wanted Clooney's face to not be completely static throughout. This is also another reference to spaghetti Westerns as Clint Eastwood - also a strong, silent character - would often be smoking a cigar.
The American's riverside idyllic spot was much more barren in real life so the production added lots of extra plants to make it perfect. Guards had to be posted by the location at night to prevent it from being eaten by wild boars.
Being a celebrated stills photographer, Anton Corbijn was constantly taking pictures during the shoot. These were all ultimately presented in his book "Inside The American".