In Classical Greek, Lethe literally means "forgetfulness" or "concealment". The Greek word for "truth" is a-lethe-ia, meaning "un-forgetfulness" or "un-concealment".

In Greek mythology, Lethe is one of the several rivers of Hades. Drinking from the river Lethe ("forgetfulness" or "oblivion") caused complete forgetfulness. Some ancient Greeks believed that souls were made to drink from the river before being reincarnated, so they would not remember their past lives.

Some private mystery religions taught the existence of another river, the Mnemosyne; those who drank from the Mnemosyne would remember everything and attain omniscience. Initiates were taught that they would receive a choice of rivers to drink from after death, and to drink from Mnemosyne instead of Lethe. These two rivers are attested in several verse inscriptions on gold plates dating to the 4th century BC and onward, found at Thurii in Southern Italy and elsewhere throughout the Greek world.

The Myth of Er at the end of Plato's Republic, tells of the dead arriving at the "plain of Lethe", which the river Ameles ("careless") runs through.

There were rivers of Lethe and Mnemosyne at the shrine of Trophonius in Boeotia, from which worshippers would drink before making oracular consultations with the god.

In the Divine Comedy, the stream of Lethe flows to the centre of the earth from its surface, but its headwaters are located in the Earthly Paradise found at the top of the mountain of Purgatory.

Lethe, the daughter of Eris ('Strife' in Hesiod's Theogony), is probably a separate personification of forgetfulness rather than a reference to the river Lethe.

In Sarah Ruhl's play Eurydice, all the shades must drink from Lethe and become like stones, speaking in their inaudible language and forgetting everything of the world. This river is a central theme of the play.