The Witch of Edmonton has frequently been read as a play which exposes the social problems that led to witchcraft accusations in early modern society. This article examines another aspect of the play which has not yet been adequately discussed by literary scholars: the role of physiology, and especially the role of human blood, in the play’s representation of witchcraft and the devil’s manipulation of human beings. In the world of the play, the devil’s ability to influence people by exercising control over the blood and its various constituents is a vital tool in his seduction of the witch, Elizabeth Sawyer. It is instrumental in her ultimate damnation, changing her both physically and temperamentally over the course of the play so that she ends up beyond salvation. The play subtly reveals the physiological roots of demonic influence and presents a new way of understanding the ‘blood pact’ made between witch and devil, representing witchcraft as a form of addiction that resembles a widespread but controversial present-day idea about drug abuse as a medical and a moral phenomenon, the brain disease model of addiction (BDMA).