Before the time of written records, early humans used plants to relieve symptoms and cure disease, forming the basis of the modern study of ethnobotany and the starting point for the history of medicinal plants. During this intensive course on the history and current directions of medicinal botany, we will track the knowledge of medicinal plants from prehistory through the spectacular work of the Renaissance herbalists, the “Doctrine of Signatures,” and the development of the European medical tradition. New World settlers carried the seeds of medicinal plants with them to North America, where European medical knowledge commingled with Native American lore. We consider the contributions of the Shakers as herb growers and purveyors and the context of herbal medicine in nineteenth century America, an era of dangerous medical practices. The new field of zoopharmacognosy and the current ethnobotanical approach to new drug discovery brings us full circle to a complete understanding of human-plant interactions and botanical cures for human disease. In closing, we consider new plant-derived medicines, their future in human medicine, and the importance of preserving the diversity of medicinal plants.