There were numerous reports of werewolf attacks – and consequent court trials – in 16th-century France. In some of the cases there was clear evidence against the accused of murder and cannibalism, but none of association with wolves; in other cases people have been terrified by such creatures, such as that of Gilles Garnier in Dole in 1573, there was clear evidence against some wolf but none against the accused.
Werewolvery was a common accusation in witch trials throughout their history, and it featured even in the Valais witch trials, one of the earliest such trials altogether, in the first half of the 15th century. Likewise, in the Vaud, child-eating werewolves were reported as early as 1448. A peak of attention to lycanthropy came in the late 16th to early 17th century, as part of the European witch-hunts. A number of treatises on werewolves were written in France during 1595 and 1615. Werewolves were sighted in 1598 in Anjou, and a teenage werewolf was sentenced to life imprisonment in Bordeaux in 1603. Henry Boguet wrote a lengthy chapter about werewolves in 1602. In the Vaud, werewolves were convicted in 1602 and in 1624. A treatise by a Vaud pastor in 1653, however, argued that lycanthropy was purely an illusion. After this, the only further record from the Vaud dates to 1670: it is that of a boy who claimed he and his mother could change themselves into wolves, which was, however, not taken seriously. At the beginning of the 17th century witchcraft was prosecuted by James I of England, who regarded "warwoolfes" as victims of delusion induced by "a natural superabundance of melancholic". After 1650, belief in Lycanthropy had mostly disappeared from French-speaking Europe, as evidenced in Diderot's Encyclopedia, which attributed reports of lycanthropy to a "disorder of the brain. although there were continuing reports of extraordinary wolflike beasts (but not werewolves). One such report concerned the Beast of Gévaudan which terrorized the general area of the former province of Gévaudan, now called Lozère, in south-central France; from the years 1764 to 1767, it killed upwards of 80 men, women, and children. The only part of Europe which showed vigorous interest in werewolves after 1650 was the Holy Roman Empire. At least nine works on lycanthropy were printed in Germany between 1649 and 1679. In the Austrian and Bavarian Alps, belief in werewolves persisted well into the 18th century.

Until the 20th century, wolf attacks on humans were an occasional, but still widespread feature of life in Europe. Some scholars have suggested that it was inevitable that wolves, being the most feared predators in Europe, were projected into the folklore of evil shapeshifters. This is said to be corroborated by the fact that areas devoid of wolves typically use different kinds of predator to fill the niche; werehyenas in Africa, weretigers in India, as well as werepumas ("runa uturuncu") and werejaguars ("yaguaraté-abá" or "tigre-capiango") in southern South America.

An idea is explored in Sabine Baring-Gould's work The Book of Werewolves is that werewolf legends may have been used to explain serial killings. Perhaps the most infamous example is the case of Peter Stumpp (executed in 1589), the German farmer, and alleged serial killer and cannibal, also known as the Werewolf of Bedburg.