Anthony Hopkins showed up on set during one of his off days just so he could watch Philip Seymour Hoffman work. The two of them shared no scenes in the film.

Philip Seymour Hoffman insisted on actually being glued to the chair during his encounter with Dolarhyde.

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Ralph Fiennes' back tattoo took eight hours to apply.

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Edward Norton says he took every penny from what he made on this film to finance La 25ème heure (2002).

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When Will Graham first encounters Hannibal Lecter in the asylum, it was originally written that Graham would show his fear of Lecter. However, Edward Norton pointed out that Graham was a seasoned and veteran agent who would never show his fear to Lecter. Brett Ratner then suggested that Graham would be afraid, but wouldn't show it, and they came up with the idea of Graham having massive armpit sweat stains following his encounter with Lecter.

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Both Sean Penn and Nicolas Cage were considered for the role of Dolarhyde.

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Many lines of Dr. Lecter in the movie are original lines of Dr. Bloom in the book.

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In William Blake's "Great Red Dragon" series of paintings, there are two with very similar names. The novel "Red Dragon," by Thomas Harris, uses the title of one painting ("The Great Red Dragon and the Woman Clothed with the Sun"), but in describing the image, gives a description of another ("The Great Red Dragon and the Woman Clothed in the Sun"). Due to the muddled reference, the first adaptation of the the novel, Le sixième sens (1986) (dir: Michael Mann), Francis Dolarhyde is obsessed with the painting that Harris cites by name, while this film features the painting as described by Harris, which is a back view of the dragon with his tail wrapped around the woman.

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When asked to reprise his role of the film, Anthony Heald wasn't sure if he'd be able to. Tim Roth became a candidate for a younger Dr. Chilton and negotiations began. At the last second, Heald became available. Interestingly enough, Roth was also considered as a possible replacement for Anthony Hopkins in Hannibal (2001), had Hopkins declined.

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Ethan Hawke was the first choice to play Will Graham.

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Michael Bay was offered the chance to direct to(?) the film.( Quoi to ? Quoi  to!!? To direct the film cé marre)

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Jack Black was considered for the role of Freddy Lounds.

Frank Langella recorded lines as the Voice of the Dragon, but his dialogue was later cut.

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In the Italian version of the film, Harvey Keitel is voiced by Ennio Coltorti, who played Commissioner Ricci in Hannibal (2001).

Director of photography Dante Spinotti also filmed the movie Le sixième sens (1986), which was the first adaptation of the novel "Red Dragon". Director Brett Ratner, who had previously worked with Spinotti on Family Man (2000), so wanted him to shoot this movie that he delayed principal photography so that Spinotti could finish shooting Pinocchio (2002).

Many actors from this film have also worked with the original Hannibal Lecter, Brian Cox. Anthony Hopkins and Mary-Louise Parker appeared with him in RED 2 (2013). Edward Norton and Philip Seymour Hoffman appeared with him in La 25ème heure (2002). Emily Watson appeared with him in The Boxer (1997) and The Water Horse (2007). Ralph Fiennes appeared with him in Ennemis jurés (2011).

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Harvey Keitel is playing a character originally played by Dennis Farina in Le sixième sens (1986). In Get Shorty (Stars et truands) (1995), Keitel played Farina's character during the 'movie within a movie'.

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The novel 'Red Dragon' by Thomas Harris was first published in 1981, ten years before Anthony Hopkins was cast as Hannibal Lecter in Le silence des agneaux (1991). Nevertheless, it would seem that Welshman Hopkins was destined to play Lecter as the emblem on the flag of Wales is of a large red dragon on a green and white field. In the Welsh language, the flag's name is "Y Ddraig Goch," meaning literally The Red Dragon.

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At the end of Hannibal Lecter's note in the Tattler to the Tooth Fairy, it says "Bless you, 666." 666 is the mark of the Beast in the Book of Revelation.