In the late 1500s, a lycanthrope was a mentally ill person who believed that he was a wolf. Popular myths and stories of humans changing into wolves gradually altered the meaning of lycanthrope to mean an actual monstrous creature.

Some scholars point to The Epic of Gilgamesh as the origin of werewolf mythology. Gilgamesh rejects the advances of Ishtar, the goddess of fertility, because she turned her previous mate into a wolf.

Much like the famous Salem witch trials, the trial and execution of supposed werewolves emerged in what is now Switzerland in the early 15th century and spread like wildfire throughout Germany, France, and the Balkans. Thousands of people were killed for their alleged wolf-related crimes, whether it be turning into a werewolf or being a "wolf charmer."

Werewolves are often immune to damage caused by ordinary weapons, but vulnerable to silver objects such as a silver-tipped cane, bullet or blade. This negative reaction is sometimes so strong that the mere touch of the metal on a werewolf's skin will cause burns.

Professor Lupin became infected with lycanthropy when he was attacked by Fenrir Greyback.

According to legend, a unibrow, tattoos, hairy palms, and a long middle finger are all signs of a werewolf. Other common traits include unusual strength, an irrational fear of water, and especially glow-in-the-dark red eyes!

Peter Stumpp was a German farmer, accused of lycanthropy, witchcraft and cannibalism. A pamphlet, originally published in London in 1590, describes Stumpp's trial and his alleged crimes. It includes statements from neighbours and witnesses who claim that Stumpp owned a belt, given to him by the devil, that allowed him to transform into the likeness of a "greedy, devouring wolf".

The idea that being bitten by a werewolf could result in the victim turning into one, suggests the idea of a transmittable disease such as rabies, which causes confusion, hallucinations, hypersalivation, and hydrophobia (fear of water). Porphyria can cause psychosis, as well as excess hair growth and disfigured skin and teeth. Inherited forms of hypertrichosis (excess hair) have been described historically as dog-men and wolf-men.

Various methods have existed for removing the werewolf form, including one Danish belief which holds that merely scolding a werewolf will cure it.

In The Wolf Man (1941), the title character is bludgeoned to death with his own silver walking stick.