During the filming of one scene, the controls for the animatronic anaconda shorted out, causing it to completely lose control. Some of the footage is included in the movie.

The Amazonian film shoot was occasionally disrupted by the fact that several cast members were deathly afraid of snakes.

The film makes mention of the Candiru, a tiny catfish (also known as the Vampirefish) which has been attributed with the peculiar behavior of swimming into the human body through the urethra (in men) or the vagina (in women), where it lodges itself with its spines. This is not as common an occurrence as the film implies. Only one such incident is known to have happened to a man where a small catfish travelled into the urethra while he was urinating in a river. This account has been corroborated by Jeremy Wade in River Monsters - Amazon Flesh Eaters.

The CGI for the anacondas cost $100,000 per second.

In the theatrical trailer, when the anaconda attacks Gary, the CGI snake had not yet been put in, so he was falling backwards with nothing grabbing him.

This film is listed among the 100 Most Enjoyably Bad Movies Ever Made in Golden Raspberry Award founder John Wilson's book The Official Razzie Movie Guide.

Gillian Anderson and Julianna Margulies turned down the role of Terri Flores.

Strong language was dubbed with (for example, using 'freaking') in order to get a PG-13 rating. Not only do the ADR'd lines have a slightly different sound to the rest of the dialogue, but the actors' and actresses' lips do not match the new dialogue when they speak.

A stationary animatronic of the anaconda featured in the movie was on display at the California Academy of Sciences in San Francisco. It's tail had the skin taken off, revealing the skeletal structure of the snake and the inner workings of the animatronic.

Contains two allusions to Ice Cube's musical career. His first line of dialogue is "Today is a good day", referring to his 1992 hit "It Was A Good Day". There is a scene of him listening to Mack 10's song "Foe Life", which he co-wrote.

Mark Haskell Smith was responsible for much of the shooting screenplay, but went uncredited for his work.

Gillian Anderson auditioned for the role of Denise Kalberg, but lost out to Kari Wuhrer.

Just after Sarone falls in the water and the character goes back to bed having saved the day, the boat moves off the rocks as the waterfall goes backwards (yes, up).

Contrary to popular rumor, the movie was not filmed in the Dominican Republic. Most of the river scenes were filmed on the Rio Negro, near Manaus, Brazil. The rest were filmed at the Los Angeles Arboretum.

Jean Reno was considered for the part of Paul Serone.

Jennifer Lopez's character was originally called Terri Porter.

Sir Sean Connery and Tommy Lee Jones turned down the role of Paul Serone.

Jennifer Aniston were considered for the role of Terri Flores.

Izabella Scorupco were considered for the role of Denise Kalberg.

Will Smith were considered for the role of Danny Rich.

John Malkovich were considered for the role of Paul Serone.

Cameron Diaz was considered for the role of Denise Kalberg.

Michael J. Fox was considered for the role of Dr. Steven Cale.

Juliette Binoche were considered for the role of Terri Flores.

Ving Rhames were considered for the role of Danny Rich.

Liam Neeson were considered for the role of Paul Serone.

Nicole Kidman were considered for the role of Terri Flores.

Tom Hanks were considered for the role of Danny Rich.

Kirk Douglas were considered for the role of Paul Serone.

Ray Romano were considered for the role of Dr. Steven Cale.

Kate Beckinsale were considered for the role of Terri Flores.

Bill Murray were considered for the role of Danny Rich.

Harrison Ford were considered for the role of Paul Serone.

Billy Crystal were considered for the role of Dr. Steven Cale.

Annette Bening were considered for the role of Denise Kalberg.

Albert Brooks were considered for the role of Danny Rich.

Kim Basinger were considered for the role of Terri Flores.

Dennis Quaid were considered for the role of Dr. Steven Cale.

Martin Sheen were considered for the role of Paul Serone.

Ben Stiller were considered for the role of Dr. Steven Cale.

Teri Hatcher were considered for the role of Denise Kalberg.

Sandra Bullock were considered for the role of Terri Flores.

Keith David were considered for the role of Danny Rich.

Jack Nicholson were considered for the role of Paul Serone.

Dave Foley were considered for the role of Dr. Steven Cale.

Gwyneth Paltrow were considered for the role of Denise Kalberg.

The "blood of monkeys" that Sarone throws to Terri and Danny was made with jelly and plum juice.