Jim Jarmusch stated in an interview that he wrote the role of Ghost Dog specifically for Forest Whitaker, and if Whitaker hadn't taken the role, the film probably would not have been made.
As the main character, Forest Whitaker doesn't have an onscreen (non-voiceover) line of dialogue until nearly 37 minutes into the film.
Ghost Dog and Louie have differing recollections of their first meeting. This is a reference to the story in Rashomon (1950) where people give varying accounts of the same event.
In several scenes in the movie the main character can be seen wearing a shirt that has Chinese writing on it. The text is from the Qing dynasty and means "All things are impermanent, this is the rule of creation and destruction, once created already extinguished, silently ending is the path to happiness." (Pin yin: zhu xing wu chang, shi sheng mie fa, sheng mie mie yi, ji mie wei yue)
Many consider this to have been a "definitive role" for Whitaker. In a manner similar to his preparation for Bird, he again immersed himself in his character's world; he studied Eastern philosophy and meditated for long hours "to hone his inner spiritual hitman." Jarmusch has told interviewers that he developed the title character with Whitaker in mind; the New York Times review of the film observed that "It's hard to think of another actor who could play a cold-blooded killer with such warmth and humanity.