According to ancient legend, as told by History of Magic Professor Cuthbert Binns, Salazar Slytherin was responsible for the construction of the Chamber of Secrets beneath Hogwarts dungeons. It was specifically created for the purpose of purging the school of all Muggle-born students. The Chamber contained a basilisk which could be controlled only by his own "true heir", and use it to rid the school of all Muggle-borns. At least part of the legend was revealed to be true in 1943, when Tom Marvolo Riddle, the heir of Slytherin, opened the Chamber and used the Basilisk to attack Muggle-borns.

One girl the Basilisk actually killed is now a ghost known by the name of Moaning Myrtle. The opening to the Chamber of Secrets is located in the bathroom she now haunts, and can only be opened by speaking Parseltongue, as Slytherin could. Riddle opened the Chamber again in 1993 through the use of one of his seven Horcruxes, his diary. Using the bit of his soul encompassed by the diary, he possessed Ginny Weasley and forced her to do his bidding. While he still attacked Muggle-born students, his ultimate goal was to lure Harry Potter into the Chamber and kill him.

Salazar Slytherin owned a locket emblazoned with the letter S that became an heirloom of his last known line of descendants, the Gaunts. Merope Gaunt sold the locket to Caractacus Burke. It was then bought up by Hepzibah Smith, who had a love for antiques. It was subsequently stolen from her by Tom Marvolo Riddle. Riddle would later turn the locket into a Horcrux, and conceal it in a seaside cave he had visited in his youth. The same locket was later removed from the cave by Regulus Black with aid from his house-elf, Kreacher. Kreacher was ordered to destroy the locket, but was unable to do so.

It was later stolen from the Black family home at 12 Grimmauld Place by Mundungus Fletcher, and eventually found its way into the hands of the Ministry of Magic employee, Dolores Umbridge. Umbridge used it as an intimidation tool by wearing it and claiming the S stood for Selwyn, a pure-blood family line. She either did not know better or wanted to conceal its real meaning from the public.

The locket was recovered by Harry Potter, and was later destroyed by Ron Weasley with Godric Gryffindor's sword. This act of destruction removed all of the Horcrux's power.

There were also portraits of Slytherin hung at Hogwarts Castle, one guarding a secret shortcut between the dungeon's antechamber and the Entrance Hall side room. The password required to gain access to said shortcut was Mortal Dread[6]. The other was hung at the Headmaster's office, part of the Headmaster portraits gallery[7].

In the 1997–1998 school year, Slytherin's heir, Riddle (now known as Lord Voldemort), realised his ancestor's wish of purging the school of Muggle-borns via another method: by taking over the Ministry of Magic and using falsified propaganda. Voldemort managed to have Muggle-borns evicted from the wizarding world, and at the end of the year, Voldemort even claimed that Hogwarts no longer needed Sorting, and that Slytherin's symbols, shields and colours would suffice. After Voldemort's death, all of this was repealed, and Slytherin's ultimate desire ended in failure.