The concept originated from three specials produced by John Cosgrove and Terry-Dunn Meurer titled 'Missing... Have You Seen This Person?', which were pitched to NBC in 1985 and aired in 1986.

Because the series incorporated paranormal mysteries, NBC News disowned it when it aired on the network and required a disclaimer before each show clarifying it was 'not a news broadcast'.

The show was hosted by three different actors during its early specials: Raymond Burr hosted the pilot, Karl Malden hosted the next two specials, and Robert Stack hosted the final four before becoming the full-time host in 1988.

In an attempt to boost female viewership during its final CBS season in 1999, Robert Stack was joined by co-host Virginia Madsen, but the effort failed to improve ratings and the show was soon canceled.

Later cable reruns of segments originally narrated by Virginia Madsen were re-dubbed with Robert Stack's voice.

In 1992, a young Matthew McConaughey was cast to play a murder victim in a Texas-filmed segment, one of his earliest on-screen roles.

Several future stars appeared as re-enactors before finding fame, including Cheryl Hines, Daniel Dae Kim, David Ramsey, Taran Killam, and Hill Harper.

The 2020 Netflix reboot has no host or narrator and is presented in 'pure documentary style', though an image of longtime host Robert Stack appears in the title sequence of each episode as an homage to him.

The show's eerie theme song was composed by Michael Boyd and Gary Remal Malkin, who won the ASCAP Award for Top TV Series twice, in 1992 and 1993, for their work on it.

The theme music was changed seven times throughout the show's history, in 1993, 1995, 1997, 1999, 2001, 2008, and 2020, with the 2020 version arranged and performed by West Dylan Thordson.

After an episode featured footage of an arsonist filming a house burning down while narrating strange commentary, viewers who recognized the house helped identify and lead to the arrest of two suspects.

A March 14, 1997 episode reenacted rapper Tupac Shakur's 1996 unsolved murder, airing just one week after the murder of Biggie Smalls.