Root digging and herb gathering has long been a part of the subsistence patterns of many rural Americans, but nowhere in the United States has it played a more important role than in the southern and central Appalachian Mountains. In the late-eighteenth and early-nineteenth centuries, American ginseng became one of the most important articles of commerce in some mountain sections, and as the production of patent medicines and botanical pharmaceutical products escalated in the mid- to late-nineteenth century, southern Appalachia emerged as the United States most prolific supplier of many other species of medicinal plants, known by the catch-all term crude botanical drugs. The region achieved this distinction due to both its legendary biodiversity and the persistence of certain common rights that guaranteed widespread access to the forested mountainsides, regardless of who owned the land. Following the Civil War, the region experienced an unparalleled root-and-herb boom that drew thousands of people into these supply chains and onto the de facto forest commons. Root digging and herb gathering became the most important way for landless and smallholding families to earn income from the forest commons. This boom influenced class relations, gender roles, forest use, and outside perceptions of Appalachia, and it began a widespread renegotiation of common rights that eventually curtailed access to some plants such as ginseng. Drawing on manuscripts, periodicals, business records, and other sources, this dissertation examines how and why Appalachia became the nations premier supplier of botanical drugs in the late nineteenth century and the how the trade influenced the way human residents of the region interacted with each other and with the forests around them. Using the analytical framework of political ecology, it uncovers a unique narrative of commodification, one shaped as much by local ecology and culture as by global markets. Indeed, the particular dynamics of Appalachias political ecology are more important to the rise of the botanical drug industry than scholars have heretofore acknowledged. Conversely, the botanical drug trade is more central to understanding Appalachian history than scholars have recognized.