This work provides an in-depth examination of early healthcare and the evolution of professional nursing in the heart of Appalachia. Existing histories of Appalachian healthcare tend to focus on physicians, with little written about the evolution of nursing in the region and the nurses' roles, experiences, and contributions. During a time when access to healthcare was limited or nonexistent, nurses played a prominent role in the health and well-being of Appalachian communities. Archival materials, reports, journals, personal letters, memoirs, and oral histories provide insight into the nurses' activities, dedication, resilience, and innovation in delivering early healthcare care to rural and isolated Appalachian communities.