Forrester originally worked with fellow "mad" genius Dr. Laurence Erhardt at the Gizmonic Institute, until they moved their operations to the bowels of Deep 13. He engineered the kidnapping of janitor Joel Robinson, shooting him into space onboard the Satellite of Love. Came the second season on Comedy Central, Erhardt met with a vague but painful-sounding fate and was replaced by the less intelligent but more commonly known TV's Frank.
According to the show's mythos, Dr. Forrester had been a mad scientist possibly since birth, when he was a member of Evilos (a mad scientist version of Webelos), where he grafted the rear end of a dog onto the rear end of a cat; he has traced his scientific ambitions back to "Oslo...I was found drunk and woozy...scratching the name "Paula Cranston" into my thigh with a nail". Other pivotal moments in his early life include a 1956 visit to "Sun Valley...[where] I was found behind the soft-serve machine, drooling over a picture of Dick Button" (Since Trace Beaulieu was born in 1958, Forrester must thus be at least a decade or so older than the actor who portrayed him.) and a visit to "the Ice Capades, [where] I was hot-riveting my kneecaps to Peggy Fleming's zamboni."
Forrester's high school career was typified by a series of humiliations, presumably contributing to his rather deranged personality. Frequently teased by classmates, he received a "shameful expulsion" from the Chess Club, suffered a "shameful shower incident" during his sophomore year, got rejected by the Swing Choir, was frequently victimized by book-dumpings after typing class, was forced to do power sit-ups in gym, and received "the revulsion, scorn, and rejection of all the pretty girls." At some point, he was struck by lightning, resulting in the white streak in his hair and mustache.
While earning his doctorate, Forrester took some undergraduate courses in Super-Villainry, and at some point he joined the Fraternal Order of Mad Science. He was a frequent attendee of the Mad Scientist Convention, although he lost the convention's invention contest each year (on one occasion his entry, "the More Painful Mouse Trap," was met only with laughter). In response to his rejections, he has blown up the convention center twice and once used incendiaries to not "actually make the building blow up, it just made it burn...really quickly."
While working at Gizmonic Institute, Forrester and his assistant sent Joel cheesy movies which he was forced to watch, in order to find a movie that would drive people mad and allow him to take over the world. In response, Joel built several robot friends to keep him company, and keep himself from being driven mad. Joel, Crow T. Robot, and Tom Servo mocked each of the movies they were forced to watch. During Joel's time on MST3K, Forrester participated in Invention Exchanges with Joel and the 'bots. He would show his invention, then Joel would show his invention.
At the end of the sixth season, Frank was assumed into Second Banana Heaven by the angel Torgo, an event that, surprisingly, deeply saddened Forrester, reacting as though he had lost his best friend, even lamenting Frank's loss with the song "Who Will I Kill?". In the seventh season, Pearl Forrester (Mary Jo Pehl) joined her son Clayton to help him out. When Trace Beaulieu left the series, she took over as the head mad, and continued sending bad movies to hapless temp Mike Nelson (played by Michael J. Nelson, who had replaced Joel halfway through the 5th season) and the 'bots.
In the final Comedy Centeral-made episode he announces that his funding has been cut, causing him to pack up Deep 13 and cut loose the Satellite of Love. The end of the episode is a parody of 2001: A Space Odyssey, in which an old Clayton tries to reach a Monolith-like giant videocassette labeled "The Worst Film Ever Made". In the final scene, he is reborn as a star child. When Pearl muses about another chance to raise her son, he utters his final words of the Comedy Central series: "Oh, poopie."
When the show moved to the Sci Fi Channel for its eighth season and the setting changed to the future year 2525, it was revealed that although Pearl had intended to do a better job of raising Clayton the second time around, she had somehow never actually gotten around to doing so and he had grown into much the same sort of adult he was before. Pearl therefore killed him by smothering him with a pillow. Oddly enough, although Pearl would've thus murdered Dr. Forrester some forty years to fifty years after the events of the previous season, when the SOL crew returned to the 20th century, it was at the same time they had left it which would mean that a second Pearl and a baby Clayton were still alive at that time. However, because MST3K is "just a show" which advises its viewers to "really just relax", this was never addressed.
In 2008, Trace Beaulieu, Joel Hodgson and Frank Conniff reprised their characters for a brief DVD skit explaining the rights issues for one of the films. The skit depicted Joel and the 'bots back on the ship and Forrester (as an adult) back at the lab with Frank. It's not known where (or if) the scene fits within the show's continuity.