The Sinister Six is one of Spiderman's greatest foes. It was started by Doctor Octopus after he escaped from prison. He wanted revenge and he then organized Spiderman's greatest foes such as Kraven, Electro, Sandman, Mysterio and Vulture. Doctor Octopus promised a plan that would ultimately doom Spiderman but he only organized the kidnapping of Better Brant as well as May Parker.

This essentially turned Spiderman into a frenzy and his rage ultimately fueled him to defeat the six. At the first time that the six came together, they chose to attack Spiderman individually, which then insured the defeat of the group.

After some years, Doctor Octopus again brought together the group and he coerced Sandman, who was also one of Spiderman's deadliest foes, to join by threatening to kill his family. If the Sandman did not cooperate, they would be dead. So with Sandman in the picture, Doctor Octopus was able to launch an attack against Parker in the form of spraying chemicals in the atmosphere. Doctor Octopus's plan was to sell the antidote for the chemical weapon that he and the Sinister Six hijacked.

After learning of Doctor Octopus's plans, the betrayed five sought revenge and wanted to get back at Doctor Octopus. The disorder within the group came to a point that Otto Octavius (Doctor Octopus) turned Sandman into glass and shattered him. Gog, who was from the Tsiln race, took the place of the Sandman and they continued their plans. Other heroes such as the Fantastic Four, the Hulk, Sleepwalker, Nova, Ghost Rider Deathlok and Solo fought the six, Sandman was able to come back, reconstituted and in an attempt to get revenge on Doctor octopus, nearly killed him.

Later in the team's history, Doctor Octopus was eventually murdered by Kaine, who was a Peter Parker clone. Because of this, the rest of the team feared Kaine and Electro, Hobgoblin, Mysterio and Vulture joined with Beetle, Shocker and Scorpia in order to form the Sinister Seven. The devious team members tried again and again to do Peter Parker but they eventually self-destructed as they fought with one another time and time again.

This was one of the most potentially powerful groups that Spiderman faced yet they failed in what they wanted to do because they could not see past their differences and they lost sight of the goal to destroy Peter parker. The Sinister Six could probably reunite again but it will still be just a faint hope for these six to finally overcome Spiderman.