When Sean mentions how hot it is, Agent Flynn responds with "I'm from Tennessee, I hadn't noticed". Samuel L. Jackson is actually from Tennessee.
The initial script for the film was 122 pages long when director David R. Ellis signed on to direct the film. After reworking the script along with his producing director and Samuel L. Jackson for more than four months, the script was narrowed down to 103 pages.
This film's title originated at an after-work happy hour among Hollywood colleagues to see who could come up with the most awful pitch for a movie. Producer Craig Berenson, who worked for DreamWorks at the time, gave his pitch for this movie based on a script called "Venom."
Most snakes were digitally created because the real snakes did not move as much as the filmmakers wanted.
The movie's line "I have had it with these motherfucking snakes on this motherfucking plane!" was voted as the #55 of "The 100 Greatest Movie Lines" by Premiere in 2007.
A live diamondback rattlesnake was found in a Phoenix, Arizona AMC theater during an August 2006 screening. Another rattler was found nearby in the parking lot.
When the male flight attendant puts the snake in the microwave, he can be seen hitting the 'snake' preset button on that microwave - a somewhat unusual preset for a microwave.
The filmmakers named the large Burmese python "Kitty".
450 snakes were used including one 22-foot-long Burmese python.
Contrary to popular belief, Samuel L. Jackson's agent insisted that the title be changed, because Jackson "couldn't" work on a film with such a title. When Jackson heard about all of this he responded with the much cited comment, "We're totally changing that back. That's the only reason I took the job: I read the title."
Ronny Yu was attached to direct, speaking enthusiastically about the project, but bowed out following budget disputes and "creative differences". He was replaced by David R. Ellis.
In March 2006 New Line Cinema, due to massive fan interest on the Internet, allowed for a 5 day re-shoot to film new scenes to take the movie from PG-13 to a R-rated film (originally the film wrapped principal photography in September 2005). Among these additions is the Samuel L. Jackson character's line, "I've had it with these motherfucking snakes on this motherfucking plane," a line that originated in an anticipatory internet parody of the movie.
The fake working title that was written on the clappers was Anaconda 3.
The phrase "snakes in the cockpit", which is said in the film, is used by pilots in reference to the high number of complex tasks they have to accomplish.