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."
(At around forty-four minutes) 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.
(At around one hour twenty-six minutes) 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.
In March 2006, New Line Cinema, due to massive fan interest on the Internet, allowed for a five day re-shoot to film new scenes to take the movie from PG-13 to an 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.
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".
In television airings of the movie, the often quoted line is changed to "I have had it with these monkey-fighting snakes on this Monday-to-Friday plane!" Ironically, Samuel L. Jackson later ended up fighting monkey type creatures in The Legend of Tarzan (2016) and Kong: Skull Island (2017).
In Aqua Teen Hunger Force (2000), season two, episode one, "Super Birthday Snake", Meatwad names his snake "Nathan (Scott) Phillips". One of the lead actors in this snake-themed movie is Nathan Phillips.
The initial script for the film was one hundred twenty-two pages long, when David R. Ellis signed on to direct. After re-working the script, along with his Producing Director and Samuel L. Jackson, for more than four months, the script was narrowed down to one hundred three pages.
In 2013, an incident happened with EasyJet Airlines in the U.K., where a man had a snake on-board which panicked all of the passengers on the flight. However, the man later confirmed the snake was not venomous and it was safely removed from the flight.