The Sinister Six are a group of supervillains in the Marvel Comics universe, who serve as a collection of Spider-Man's greatest foes. The original incarnation of the Sinister Six appeared in Amazing Spider-Man Annual #1 (1965).

The original lineup of the Sinister Six consisted of Doctor Octopus, Electro, Kraven the Hunter, Mysterio, The Sandman, The Vulture. Years later the team reformed; The Hobgoblin filled the spot of Kraven, who by that point had taken his own life. The alien called Gog, the Beetle, Scorpia , the Shocker and Venom and Kraven's son and namesake have all been members of the Sinister Six.

A six-member supervillain team appears in the forthcoming Identity Disc miniseries, though whether or not this team is to be called the Sinister Six remains unseen.

In the Ultimate Marvel Universe an Ultimate Six consisting of the Green Goblin, Doctor Octopus, Kraven the Hunter, Electro, and The Sandman (who tried to recruit Spider-Man as their sixth member) went up against Nick Fury and The Ultimates after the villains escaped the S.H.I.E.L.D. prison they were held in after each had been defeated by Spider-Man and arrested by S.H.I.E.L.D. for illegally altering their genetics codes.