For centuries, human beings have been ingesting mind-altering, psychoactive substances for spiritual, medicinal, and recreational purposes. Fungi such as Amanita muscaria were ingested as far back as the neolithic period and are thought to have been used as a part of religious ceremonies for the last 4000 years. Alcohol is likely to have been consumed in neolithic China as far back as 10,000 BC, and in the time since, it became an increasingly ubiquitous facet of human life as it has descriptions of what we now consider disordered use. In the time since, we have sought to reconcile the pleasure and harm that can result from the use of such substances. The Ancient Mesopotamian, Egyptian, and Greek mythology all provided divine explanations for alcohol and its effects and, in the case of Greek mythology, used Dionysus to depict alcohol as capable of eliciting brutishness and brilliance. Later, early Christianity described alcohol as a divine gift and the excessive use of it within the moral framework of sin. All the while, nascent descriptions of excessive alcohol use as a malady was developed largely as a Galenic imbalance of humors. Anthony Benezet published A Mighty Destroyer Displayed which signified a shift to alcohol itself as being an inherent evil, largely the result of distillation. A modern disease concept finally began to take form following publications by Benjamin Rush and Thomas Trotter in the late eighteenth century describing excessive alcohol use as a disease—a concept that continued to develop throughout the nineteenth century. The demonization and criminalization of psychoactive substances throughout the twentieth and twenty-first centuries have continued to shape the role of these substances in society and our conception of addiction as a disease, in no small part due to the emphasis and investment in research and clinical care by a growing number of addiction-trained professionals which continues to grow to this day.