Three main actors from the television series, David Duchovny, Gillian Anderson, and Mitch Pileggi, reappear in the film to reprise their respective roles as Fox Mulder, Dana Scully, and Walter Skinner.

The film was first anticipated in November 2001 to follow the conclusion of the ninth season of the television series, but it remained in development hell for six years before entering production in December 2007 in Vancouver, British Columbia, Canada.

Dana Scully, a former FBI Special Agent, is now a staff physician at a Catholic hospital; she is treating Christian, a young boy with symptoms similar to Sandhoff disease.

FBI Special Agent Mosely Drummy approaches Scully for help in locating her former partner, Fox Mulder, who has been in hiding as a fugitive for several years.

The duo is taken to Washington, D.C., where Special Agent in Charge Dakota Whitney requests Mulder's expertise with the paranormal as they have been led to a clue, a severed human arm, by Father Joseph Fitzpatrick Crissman.

After a grueling nighttime search in a snow-covered field, he leads the FBI to what turns out to be a frozen burial ground of people and body parts.

Analysis of the remains, along with tracking down the recent movements from the second abducted woman's car crash, eventually leads them to Dacyshyn, an organ transporter in Richmond, Virginia, and his husband, Franz Tomczeszyn, who was among the youths Father Joe sexually abused.

During an FBI raid on the organ donor facility where Dacyshyn works, he escapes, leaving Bannan's severed head at the scene.

He drives Scully's car to Nutter's Feed Store in a small town near the abductions, as the human remains contain acepromazine, an animal tranquilizer.

Scully, unable to reach Mulder on his cell phone, contacts her old FBI superior, Assistant Director Walter Skinner, for help.

On March 27, 2008, the horror film site Bloody Disgusting reported a bootleg video of the official trailer uploaded by a user on YouTube.

The decision to shoot in Vancouver, where the first five years of The X-Files had been filmed and produced before the series had moved to Los Angeles, was an early idea—one that seemed right to both Chris Carter and David Duchovny.

Frank Spotnitz said that "In terms of making of the movie, we've brought together as many people as we can, not just from The X-Files but from all the shows that we did here in Vancouver – Harsh Realm, Millennium and The Lone Gunmen – and our crew is populated with all these faces that we'd worked with, over the past fifteen years.

Although the location is shown in exterior shots incorporated into the scene in which Fox Mulder (Duchovny), Whitney (Amanda Peet), Drummy (Alvin "Xzibit" Joiner), and Father Joe (Billy Connolly) drove to the missing agent's home, the same scene also includes footage of the actors that was filmed on a stage, using a rear projection to show the exterior from inside the car.

During filming, Carter placed a carrot juice bottle on the table of the set, having just finished the drink, as he thought it would be "a nice sort of Mulder touch."

[19] The exterior of the dorms for habitual sex offenders where Father Joe lives was an apartment complex in Vancouver that was slated for demolition while the production crew were filming there.

[25] When composing the score for I Want to Believe, Snow called it "different" from the previous film which followed the shows mytharc storyline about the government conspiracy and aliens.

He said it was much "more heart, warmth and tuneful music" since this film was based more around Fox Mulder (David Duchovny) and Dana Scully's (Gillian Anderson) relationship.

He used no trumpets and no high woodwinds when recording, but used up to eight french horns, five trombones, two pianos, one harp, thirty-two violins, sixteen violas, twelve cellos and eight basses.

The website wrote of the critics' consensus, states: "The chemistry between leads David Duchovny and Gillian Anderson do live up to The X-Files' televised legacy, but the roving plot and droning routines make it hard to identify just what we're meant to believe in.

[42] Frank Lovece of Film Journal International, likewise said, "What plot there is plays like a PG-13 Se7en: body parts, gruesomeness, gloom and doom, but hey, not too much, and don't worry, there's nothing deeply upsetting", and while praising the cinematography, music and Gillian Anderson's performance, believes, "It seems unlikely that this franchise will reach The X-Files X".

"[45] M. A. Crang, in his book Denying the Truth: Revisiting The X-Files after 9/11, praised the acting, locations and characterization, but felt that the script was the film's "biggest weakness".

[46] Roger Ebert gave a positive review of the film with three-and-a-half out of four stars, saying; "It involved actual questions of morality, just as The Dark Knight does.

[41] Sandra Hall of the Sydney Morning Herald was more equivocal, saying, "... it just about works, thanks to Carter's sense of timing and the script's allegorical enhancements.

"[47] Empire gave the film three stars ("good"), but expressed a desire for Chris Carter to return to the more comedic and "post-modern" elements of the series upon the next revisit.

If Fight The Future, which dealt in grandiose fashion with the series’ convoluted alien myth arc, was The X-Files in summer blockbuster mode, I Want to Believe was its attempt at an intimate chamber drama — more Ingmar Bergman than Michael Bay.

[53][54] Fox Chairman Tom Rothman, responding to an interview question regarding the possibility of a third X-Files movie, said in October 2008, "It's really up to Chris [Carter], David [Duchovny] and Gillian [Anderson]".

"[56] Frank Spotnitz responded to his blog readers' requests for clarification regarding Anderson's comments by denying that any deal was in place, saying, "I'm afraid I have no news to report other than our continuing desire to make a third film if there's an audience for it.

[61] Speaking at San Diego Comic-Con in July 2013, Carter, when asked about a third film, was extremely noncommittal, indicating there was still no forward movement, and saying, "We can get to it later.

[63] In March 2015, it was confirmed that there would be a six-episode miniseries on Fox, featuring Duchovny, Anderson, and some other members of the original cast, which would have both standalone and mythology elements.