Creator Glenn Gordon Caron said the inspiration for the series came from a production of The Taming of the Shrew he saw in Central Park starring Meryl Streep and Raúl Julia, which the show later parodied in the season-three episode 'Atomic Shakespeare'.

The series was created after ABC executive Lewis H. Erlicht, impressed by Caron's work on Taxi and Remington Steele, asked for a detective show with a major star; Caron wanted to do a romance and Erlicht replied he didn't care what it was as long as it was a detective show.

Cybill Shepherd described the show's rapid-fire dialogue style as 'Hawksian' during her first meeting with the producers, and suggested they screen Twentieth Century, Bringing Up Baby, and His Girl Friday to understand the overlapping dialogue technique she meant.

Glenn Gordon Caron had to fight ABC executives to cast Bruce Willis, testing him among over 2,000 actors, because the network doubted audiences would believe sexual tension between him and Cybill Shepherd.

Curtis Armstrong was brought in as Herbert Viola based on his work in Revenge of the Nerds and Better Off Dead, with the character created to give receptionist Agnes DiPesto a love interest and ease pressure on the two leads.

Orson Welles delivered the black-and-white disclaimer introduction for the episode 'The Dream Sequence Always Rings Twice,' which aired just a few days after his death, marking his final screen appearance.

To achieve a 1940s cinematic look, director of photography Gerald Finnerman and Caron banned zoom lenses in favor of slower master camera tracking shots, and used diffusion disks to soften Cybill Shepherd's features while keeping Bruce Willis sharp in the same shot.

Moonlighting scripts ran nearly twice the length of a typical one-hour drama due to the fast overlapping dialogue, and episodes took 12 to 14 days to shoot compared to the usual seven, often with dialogue written the same day it was filmed.

The black-and-white dream-sequence episode was actually shot on black-and-white film stock rather than shot in color and desaturated, specifically so the network could not later reuse it in color; the shoot took 16 days and cost about $2 million, roughly double a typical episode's budget.

Production delays became so notorious that ABC ran an ad campaign showing network executives impatiently waiting for new episodes, and one episode even featured TV critic Jeff Jarvis recapping the plot because it had been so long since the last new installment aired.

The show poked fun at its connection to Remington Steele by having Pierce Brosnan cross networks for a cameo as Remington Steele, and it acknowledged Hart to Hart as an influence by having Lionel Stander reprise his role as Max in an alternate-reality sequence.

Bruce Willis's real broken clavicle from a skiing accident and Cybill Shepherd's real-life pregnancy with twins both caused major production delays, prompting writers to shift focus onto supporting characters Agnes and Herbert in season four.