Hugh Dancy was screen tested for the role of Hannibal and would later go on to star as Will Graham in the T.V. show "Hannibal" which acted as a prequel to Red Dragon. Even then he still didn't get to play the famed cannibal, the role went to Danish actor Mads Mikkelsen.
Thomas Harris's source novel was released two months prior to the film's release. He had worked on it as well as the screenplay concurrently, for fear that a Lecter prequel/origin story would inevitably be written without his involvement. Film producer Dino De Laurentiis said "I say to Thomas, 'If you don't do [the prequel], I will do it with someone else... I don't want to lose this franchise. And the audience wants it...' He said, 'No. I'm sorry.' And I said, 'I will do it with somebody else.' And then he said, 'Let me think about it. I will come up with an idea.'"
While Lecter injects himself with sodium thiopental, he plays Johann Sebastian Bach's "Goldberg Variations" in the background, the same music that plays during his escape in The Silence of the Lambs (1991). The recording was made in 1955 by Glenn Gould. In the other movies featuring Hannibal Lecter, Gould's 1981 recording is used.
Peter Webber wanted Mikael Persbrandt for the role of the soldier who eats Hannibal Lecter's little sister, but Persbrandt had at that time already signed on for another film, and was busy with a play in Sweden.
Though not stated in the film, according to the novel the film is based on, when Hannibal drives off in the car at the film's conclusion, he's driving to Baltmore to study psychology. This sets up the events in Red Dragon (2002).