This work provides an in-depth examination into early healthcare and the evolution of professional nursing in the core of Appalachia. Most of the history of healthcare in the Appalachian region has focused on physicians, while little has been written about the evolution of nursing and the nurses' role, experiences and contributions to the region's healthcare. During a time when access to healthcare was limited or non-existent, nurses played a prominent role in the health of communities within the core of Appalachia. In addition to archived materials, an examination of reports, journals, personal letters, memoirs, and oral histories of the nurses' own thoughts and experiences provides insight to their dedication, resilience, and innovation in delivering early healthcare care to communities throughout the rural and isolated Appalachian core region.