It was CBS Productions' final series before folding into CBS Paramount Television with the merger of Paramount Television for the second season in 2006 (the CBS Productions name would be re-activated in 2008 when 90210 premiered).

The show's title is a reference to the main character Melinda Gordon (portrayed by Jennifer Love Hewitt), who lives in the town of Grandview, New York with her husband Jim (David Conrad), a medic from Mercy Hospital, and who has the ability to see and communicate with the dead. The show is also one of several fantasy television programs about young women with gifts for supernatural communication such as the NBC show Medium, and canceled shows Joan of Arcadia, Tru Calling, 1-800-Missing, Wonderfalls and Afterlife.

Season two of Ghost Whisperer premiered on September 22, 2006 and ended on May 11, 2007, again airing Friday nights on CBS during the same timeslot. CBS officially renewed the show for a third season placing it in its regular Friday 8 p.m. time slot. (Eastern US Time) The third season premiered September 28, 2007. Due to the writers strike 12 episodes were completed before the strike. However, once the strike ended, CBS has announced that the show would return April 4, 2008 with 6 episodes. On February 15, 2008, CBS renewed Ghost Whisperer for a fourth season.

Ghost Whisperer will be broadcast in reruns, not only on ION Television, but also on Sci Fi and WE TV.

It was announced on June 12, 2008 that Jamie Kennedy would join the cast as a psychology professor Eli for the fourth season of Ghost Whisperer and Jay Mohr would be leaving after appearing in the first episode in season four as his character Professor Rick Payne takes a sabbatical. Previously recurring cast member Christoph Sanders also joined the regular cast at the start of the fourth season. The fourth season of Ghost Whisperer premiered on Friday, October 3, 2008 and will consist of 26 episodes.

Ghost Whisperer is an episodic series that follows the life of Melinda Gordon, a young woman who has the ability to see and communicate with the dead. Each episode deals with one or more ghosts seeking Melinda's help in relaying a message or completing a task that will put the spirit to rest, and allow them to "cross over" into The Light, a metaphor presented by the show as its conception of Heaven. Crossing over is when a spirit leaves earth and goes to heaven.

Despite the episodic structure of the show, plot lines that span two or three episodes (normally during season openers and finishers) develop and progress throughout the rest of the season. The first season arc introduced the show's first antagonist, Romano, a negative entity in a black hat, who attempted to do the exact opposite of Melinda and gather earthbound souls and bring them to the Dark Side. The story climaxed in the season finale when a plane crashed in Grandview, and Melinda and Romano both attempted to sway the souls to the Light, and staying on earth, respectively. Her best friend Andrea Moreno was killed in the plane crash and, in a story that would carry over to the second season, was being swayed by Romano to stay earthbound.

In the second season, two new characters (Delia Banks and Professor Rick Payne) are introduced, both of whom, by season's end, come to learn of Melinda's power and become survivors that ghosts want messages passed to through Melinda. The second season arc revolves around the thinning "veil" between the living and the dead, evident in certain situations in second season episodes. By the end of the season, a second Ghost Whisperer was introduced. His arrival in Grandview sets the final events of a disastrous prophecy in motion, and the strengthening of the dark side over the Light.

The beginning of each episode normally revolves around Melinda first encountering the ghost(s) that will be crossed over in the episode. In their normally brief appearances, Melinda collects clues she later researches. After gaining a significant piece of information that drives the episode's plot further, the ghost(s) normally open up to her, and tell her how it is she can help them find peace. Often, the messages the ghosts want Melinda to pass are confusing and as a result, she is normally met with questions and scepticism by those she is trying to give the message to the families, friends and lovers of the ghosts. By the end of each episode, Melinda is usually able to complete her task and cross over the ghost(s) from the respective episode.