The original title for this series was "Please Stand By," but because the Cuban Missile Crisis had happened less than a year earlier, executives thought it might make people fearful of an air raid. As a reference to this, when The Outer Limits (1995) would cut to a commercial, the Control Voice said, "Please stand by."

The first season finale, The Forms of Things Unknown (1964) (starring David McCallum, Vera Miles, Cedric Hardwicke, and Barbara Rush), was supposed to be a pilot that series creator Joseph Stefano presented to network executives. When it was rejected, he used it as an episode of this series.

Many scenes and some entire episodes of the series were filmed on-location at series creator Joseph Stefano's house, called "Villa Di Stefano," from which the production company took its name.

Numerous guest stars on the show had been victims of the blacklist a decade earlier. For many of them, this was their first work before a camera in years. Among them were Jeff Corey, Marsha Hunt, Curt Conway, Lloyd Gough, Howard Da Silva, and Sam Wanamaker.

Dominic Frontiere and Robert Van Eps scored the first season of this series. Frontiere composed new music, as well as re-used his music from previous television shows, such as Stoney Burke (1962). The second season was scored by Harry Lubin, who also composed new music, and re-used his music from previous television shows, such as One Step Beyond (1959).