In this study, I examine the history of the association of literature and drugs. In a series of essays I explore the history of opiates, anesthetics, cannabis, stimulants and psychedelics, and ...provide an account of how each substance was described in literature. I show the ways in which historical, scientific and literary elements are interconnected in the concept of drugs, and I argue that each drug or group of drugs has a discourse that is specific to it. I show that there are literary discourses that make use of psychoactive substances throughout history (for example, the figure of Circe in Renaissance epic poetry or hashish in medieval Islam), but that the notion of a writer “experimenting” with drugs is specific to the post-Romantic era. The emergence of drug literature can be traced to a set of unusual alliances between medical researchers, philosophers and writers (Novalis, Sir Humphry Davy, De Quincey, Baudelaire and William James) and is the result of the growing divide in the nineteenth century between a scientific discourse about nature on the one hand, and a post-Kantian aesthetic discourse that explores the nature of subjectivity on the other hand. Drug literature is a hybrid genre in which the forbidden but necessary fusion of nature and culture, which is an essential part of the human condition, finds expression. As laws forbidding drug use come into effect at the beginning of the twentieth century, drugs become part of a culture of transgression and sensation that plays a crucial role in literary movements such as the avant-garde (Artaud, Junger, Michaux and Burroughs) and popular genre fiction and journalism (Dickens, Rohmer and Hunter S. Thompson). I conclude with an examination of Prozac and Ecstasy in contemporary literature and the role of drug literature in a society increasingly dominated by biochemical discourse.