- Blooper: The desert scene where they are driving the RV, look closely at the front windshield to see the camera crew.
- Dyeing for Your Art: The already slender Penélope Cruz lost six pounds to play the part, and looks skeletal. Johnny Depp also dyed his hair blonde and later red.
- Fake Nationality: Cliff Curtis, a Polynesian Maori from New Zealand, plays Columbian Pablo Escobar.
- Throw It In!: A lot of Johnny Depp's dialogue was improvised, including the scene where they are trying to find a place to put all their money from selling coke and his line "We're gonna need a bigger boat".
- What Could Have Been:
- John Leguizamo was offered a role in this film, but turned it down because he was already working on Moulin Rouge!.
- Denis Leary was originally cast as Derek Foreal.
- James Gandolfini was considered for Fred Jung.
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