The show centers on FBI special agents Fox Mulder (David Duchovny) and Dana Scully (Gillian Anderson) who work on cases linked to the paranormal, called X-Files.

At work the next day, Ed hears a woman calling him a "loser"; he has a violent confrontation with a female co-worker—who denies saying anything—and is subsequently subdued.

In Washington, Agents Fox Mulder and Dana Scully conduct a discreet meeting with a Russian informant, Vsevlod Pudovkin, who claims to have seen a UFO at a secret research center.

Upon returning to FBI headquarters, Mulder heads out on vacation to visit Graceland, leaving Scully to follow up on the Pudovkin case for him.

Upon hearing the voice after a pair of Jehovah's Witnesses stop by, Ed goes downstairs and murders his neighbor, throwing her body in the furnace.

That night, Scully talks to Mulder over the phone and informs him that Pudovkin is a con man and part of the Russian mafia.

Ed was brought to a burn center in Philadelphia where the doctors found ergot derivatives in his blood, probably from contaminated dyes in the ink used by the tattoo parlor.

[1] "Never Again" was written by writing partners Glen Morgan and James Wong, making it their final episode of The X-Files until they returned to the show during its tenth season; following this episode, the two took over as executive producers of the Fox program Millennium (developed, like The X-Files, by Chris Carter).

[2] The initial story the two developed was a "sort of Abraham Lincoln's ghost in the White House type of thing",[3] which would have involved Mulder and Scully investigating the haunting.

[4] However, due to the massive amounts of rewrites the two were forced to do for "Musings of a Cigarette Smoking Man", both Morgan and Wong lost interest in their original story.

[6]Initially, Anderson called up Morgan and asked him to write a story in which Scully "fall[s] hard" for another man, leading to an "intense kind of romantic or passionate relationship".

Anderson has said that she "would have played the part [in 'Never Again'] differently" had she been aware of this at the time, as Scully discovers that she has cancer at the end of "Leonard Betts".

[6] The actor who portrays Ed Jerse, Rodney Rowland, was a former cast member of Glen Morgan and James Wong's short-lived Fox series Space: Above and Beyond.

[8] Anderson initially volunteered to get a real Ouroboros tattoo for the episode, but she was later told by the production crew that it would "have taken too long [and] it wouldn't have been practical.

"[9] Kristina Lyne from the show's art department thus designed several stick-on decals that emulated the look of real tattoos.

[12] He was, however, critical of Mulder's actions in the episode, calling him a "spoiled ass" and noted that there was a "little boy ignored feel to his dialogue at the end".

[12] Meghan Deans from Tor.com wrote positively of the episode and noted that "[i]t is fortunate, I think, that the Super Bowl forced the change in sequence.

[14] Vitaris, however, was critical of the "Leonard Betts"/"Never Again" switch, writing that "nothing in this episode points to fear of cancer as Scully's motivation".

Robert Shearman, in his book Wanting to Believe: A Critical Guide to The X-Files, Millennium & The Lone Gunmen, on the other hand, gave the episode a mixed review and rated it two-and-a-half stars out of five.

[15] Shearman argued that Scully's belief that her life is boring is easily countered by the fact that "she hunts fluke monsters, catches serial killers, and gets abducted by aliens".