The Hitchhiker's Guide to the Galaxy is a comedy science fiction franchise created by Douglas Adams. Originally a 1978 radio comedy, it was later adapted to other formats, including novels, stage shows, comic books, a 1981 TV series, a 1984 text adventure game, and 2005 feature film. The various versions follow the same basic plot. However, in many places, they are mutually contradictory, as Adams rewrote the story substantially for each new adaptation. Throughout all versions, the series follows the adventures of Arthur Dent and his interactions with Ford Prefect, Zaphod Beeblebrox, Marvin the Paranoid Android, and Trillian.

Arthur Philip Dent, accompanied by Ford Prefect, barely escapes the Earth's destruction when it is demolished to make way for a hyperspace bypass. Arthur spends the next several years, still wearing his dressing gown, helplessly launched from crisis to crisis while trying to straighten out his lifestyle. He rather enjoys tea, but seems to have trouble obtaining it in the far reaches of the galaxy. In time, he learns how to fly (not in an airplane—but by throwing himself at the ground and missing) and carves a niche for himself as a sandwich maker. He is also worried about "everything."

Ford Prefect is Arthur Dent's friend. He rescued Dent when the Earth is unexpectedly demolished to make way for a hyperspace bypass at the start of the story. Although his heart is in the right place and he is shown to be highly intelligent, resourceful, and even brave, Ford is essentially a dilettante when it comes to causes such as the search for the question to the ultimate answer of "life, the universe, and everything." Ford takes a more existential view of the universe, sometimes bordering on joyful nihilism. He is eccentric and broad-minded – no doubt due to his vast experience of roughing it around the galaxy – and has an off-key and often very dark sense of humour.

Zaphod Beeblebrox is a "semi-half-cousin" of Ford Prefect. He is hedonistic and irresponsible, narcissistic, and often extremely insensitive to the feelings of those around him. Zaphod invented the Pan Galactic Gargle Blaster. Zaphod wears unique clothing that contains a mixture of bright and contrasting colours to make him stand out and be the centre of attention wherever he goes. He was voted "Worst Dressed Sentient Being in the Known Universe" seven consecutive times. He's been described as "the best Bang since the Big One" by Eccentrica Gallumbits, and as "one hoopy frood" by others. He was briefly the President of the Galaxy and is the only man to have survived the Total Perspective Vortex (In the artificial galaxy created by Zarniwoop).

Marvin the Paranoid Android is the ship's robot aboard the starship Heart of Gold. Built as one of many failed prototypes of Sirius Cybernetics Corporation's GPP (Genuine People Personalities) technology, Marvin is afflicted with severe depression and boredom, in part because he has a "brain the size of a planet" which he is seldom, if ever, given the chance to use. Indeed, the true horror of Marvin's existence is that no task he could be given would occupy even the tiniest fraction of his vast intellect. Marvin claims he is 50,000 times more intelligent than a human.

Trillian (Tricia McMillan) is a mathematician and astrophysicist whom Arthur Dent attempted to talk to at a party in Islington. She and Arthur next meet six months later on the spaceship Heart of Gold, shortly after the Earth has been destroyed to make way for a hyperspace bypass.

Slartibartfast is a Magrathean, and a designer of planets. His favourite part of the job is creating coastlines, the most notable of which are the fjords found on the coast of Norway on planet Earth, for which he won an award. When Earth Mk. II is being made, Slartibartfast is assigned to the continent of Africa. He is unhappy about this because he has begun "doing it with fjords again" (arguing that they give a continent a lovely baroque feel), but has been told by his superiors that they are "not equatorial enough". In relation to this, he expresses the view that he would "far rather be happy than right any day."

Agrajag is a tragic and piteous creature who is continually reincarnated and subsequently killed, each time unknowingly, by Arthur Dent. Agrajag is first identified in the novel Life, the Universe and Everything; however, it is revealed that several of Arthur's encounters in the first and second novels (and in previous chapters of the third) were with previous incarnations of Agrajag. The first occurs in the novel The Hitchhiker's Guide to the Galaxy, when a bowl of petunias is yanked into existence miles above the planet Magrathea in place of one of the missiles targeting the Heart of Gold after its Improbability Drive is used, and begins falling, having only time to think "Oh, no, not again" before crashing to the ground. The Guide states that "many had speculated that if we knew exactly why the bowl of petunias had thought that, we should know a lot more about the nature of the universe than we do now". The reason behind the bowl's lament is revealed in the novel Life, the Universe and Everything, when Agrajag identifies the bowl of petunias as one of his prior incarnations, and tells Arthur that he had seen his face in a spaceship window as he fell to his doom. In another incarnation, Agrajag was a rabbit on prehistoric Earth (during the time period recounted in the novel The Restaurant at the End of the Universe) who was killed by Arthur for breakfast and whose skin was fashioned into the pouch Arthur is still carrying, which is then used to swat a fly who also happened to be Agrajag. In yet another, near the beginning of the novel Life, the Universe and Everything, Agrajag is an old man who dies of a heart attack after seeing Arthur and Ford materialise, seated on a Chesterfield sofa, in the midst of a match at Lord's Cricket Ground.