Physicist Michio Kaku noted in his book The Future of the Mind that Sliders began when a young boy read his book Hyperspace, though he said he takes no responsibility for the physics behind the series.

Speculation arose that Sliders was inspired by George R. R. Martin's 1992 unaired ABC pilot Doorways, which also featured fugitives fleeing through parallel worlds with a device indicating when the next portal would open; Martin clarified it was Tormé's agent, not Tormé himself, who had inquired about a writing position on Doorways, and Tormé denied any connection between the two shows.

While filming the episode 'Desert Storm', actor Ken Steadman, who played Cutter, was killed instantly when a dune buggy he was moving between takes overturned and crushed him; his parents said the death was preventable.

For its first two seasons the series was produced in Vancouver, British Columbia, but Fox shifted production to Los Angeles in season three to cut costs, forcing the dropping of several recurring characters who would have been too expensive to fly in from Vancouver.

John Rhys-Davies, the first main star to leave the show, said the writers often 'looted' ideas from other films rather than paying tribute, citing episodes resembling Tremors, Twister, Night of the Living Dead, and even reusing the original masks from The Island of Doctor Moreau.

Rhys-Davies said his breaking point came when he saw the writers watching a DVD of the film Species and discussing lifting scenes directly from it for use in the show.

Sabrina Lloyd did not return for the show's revival on Sci-Fi partly due to a personal falling-out with Kari Wuhrer and a salary dispute; her character's fate of being trapped in a Kromagg breeding camp was reportedly the idea of executive producer David Peckinpah alone.

The Sci Fi Channel's strict rule against showing a gun pointed at a person's head was seemingly ignored when producer Bill Dial deliberately submitted scripts featuring a character's head being shot off and the unresolved finale cliffhanger, both of which went uncorrected.

The Family Guy episode 'Road to the Multiverse' was originally going to be titled 'Sliders' before release.