The Eastern Band of the Cherokee Indians live in one of the planets most floristically diverse temperate zone environments. Their relationship with the local flora was initially investigated by James Mooney and revisited by subsequent researchers such as Frans Olbrechts, John Witthoft, and William Banks, among others. This work interprets the collective data recorded by Cherokee ethnographers, much of it in the form of unpublished archival material, as it reflects the Cherokee ethnobotanical classification system and their medical ethnobotany. Mooneys proposed classification system for the Cherokee is remarkably similar to contemporary models of folk biological classification systems. His recognition of this inherent system, 60 years before contemporary models were proposed, provides evidence for their universality in human cognition. Examination of the collective data concerning Cherokee medical ethnobotany provides a basis for considering change in Cherokee ethnobotanical knowledge, for reevaluation of the statements of the various researchers, and a means to explore trends that were not previously apparent.