The show is filmed entirely on the Universal Studios back lot in Hollywood. The town square is the same central place that was used in the Back to The Future trilogy. Subsequentially, Tom Wilson who played Biff Tannen in the trilogy has been known to pop up now and then in the show.
Cesar Millan (also known as the "Dog Whisperer"), has featured a couple of times in the Ghost Whisperer series. During the first season episode "Dead Man's Ridge", the character Andrea was twice seen reading a book written by him. Then in the second season episode "Children of Ghosts", Cesar makes a cameo appearance as himself.
The name of Melinda's store might be a reference to Jennifer Love Hewitt also being a singer: Melinda's shop is called "Same as it never was." In 1999 Jennifer Love Hewitt released a song called "How do I deal," in which she sings the line "same as it ever was.", a line which is also sung in the Talking Heads song, "Once In A Lifetime".
Director John Gray is from Bay Ridge, Brooklyn originally and in many of the episodes there are references to streets and locations from Bay Ridge Brooklyn (example, Lento's Restaurant in the movie was the name of an actual Bay Ridge restaurant for over 30 years).
Jennifer Love Hewitt was offered the role in The Ring (2002), of Rachel Keller, but turned it down. This character, like her "Ghost Whisperer" character Melinda, has a son named Aidan who is sensitive to the paranormal.