The series initially starred Gloria Reuben as Brooke Haslett, the skeptical partner of Jess. Other stars of the series during its first season included Justina Machado as Sunny Estrada, and Dean McDermott as Alan Coyle.

In the second season, significant changes, including casting, were made. The show was completely retooled. The partner of Jess was changed to Nicole Scott, played by Vivica A. Fox. Taking the place of Sunny was All My Children star Mark Consuelos and Justin Louis assumed the role of the tough Assistant Director John Polluck. The psychic powers of Jess remain important, but there is more attention payed to the other characters.

This is based on the 1-800-WHERE-R-YOU series by Meg Cabot.

Thought only to be the end of the season, the series finale aired on February 5, 2006 alongside the show's partner Strong Medicine and April 2006, word reached the public that Missing had been cancelled after a successful three year, 56-episode run. Lifetime said the show had "run its course."

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