There are about 2,000 entities in the world today that ethnologists call societies, each with distinct cultures. Perhaps the most obvious marker, and many argue the most important, is that each of these entities has its own language. Among the other societal attributes, besides language, that can make claims to human universality, or nearly so, is the cultural use of psychoactive substances— or what commonly are referred to as simply “drugs.” These range from mild stimulants such as coffee, tea, cacao, coca, and kola to stupeficients such as opium and alcohol, to hallucinogens found in mushrooms, cacti, and a number of flowering plants. Since the Mesolithic and perhaps before, the vast majority of the world’s peoples have used one or more such substances for religious and related purposes. Even in their most seemingly secular contexts, drugs are often used in ritual and habitual ways that exhibit their cultural embeddedness. Increasingly the world’s remaining indigenous peoples and many local folk are confronting questions and the consequences of the production, processing, trade, trafficking, and consumption of drugs deemed illegal and illicit by global agencies and national polities. Some of these substances, usually in their unrefined forms, have deep roots in local and indigenous cultures and economies. Often they serve important roles in constituting and maintaining cultural identity. With ever-increasing modernization and globalization, the circumstances and conditions under which indigenous and local peoples produce, trade, and use these substances continues to change. In turn, psychoactive substances—whether sanctioned, proscribed, or both—often serve as agents in the creation and defense of local and indigenous “moral” geographies. The concept of moral geography (as used here) refers to both the actual and symbolic terrain upon which traditional societies elaborate their customary livelihood and belief systems, and the cognate spaces in which they defend these practices and perceptions. For most indigenous peoples, the drugs in their culture, whether sacred or profane, are manifest in both their moral economies and geographies. For some groups, drugs become defining elements in their relations with dominant cultures and polities. For others, they are less than determinate, but still play significant roles in mediating exchanges—both symbolic and material. In either case, they can serve as mechanisms of subordination, or modes of resistance, or sometimes both.