The early Caribbean was made distinctive by the medical challenges facing its inhabitants and by the medical practices and communications that European colonists and enslaved Africans employed to meet those challenges. Classical western philosophies indicated that the Caribbean was uninhabitable: located in a tropical zone, it was characterized by extreme heat that, if it was capable of producing great mineral wealth, was hostile to life. These theories were revised when Spanish explorers found the Caribbean to be habitable: natural historians paired accounts of natural fecundity with reports of horrible illnesses and rotting flesh. Furthermore, the transatlantic slave trade and plantation slavery introduced unprecedented challenges of maintaining the health of a huge labor force as enslaved Africans were transported across the Atlantic. The peoples who met in the Caribbean brought a variety of medical practices and conceptions of disease with them, and they adapted this prior knowledge to their new contexts. Studies of medicine in the Caribbean initially paired a transatlantic framework with a consideration of the role of disease in shaping mortality rates and the dynamics of the slave trade. More recently, scholars have revised the earlier emphasis on disease and slave mortality by examining interchanges of knowledge between African slaves and European colonists. This essay builds upon and broadens existing disciplinary and methodological approaches to medicine and disease in the early Caribbean by focusing on the medical communications with which British colonists and enslaved Africans responded to unfamiliar illnesses and curative procedures. The literatures of the early Caribbean not only grapple with unfamiliar illnesses but also manifest attempts, by European colonists and Africans alike, to respond to the multiple medical cultures present in the West Indies. I focus on three texts: physician Hans Sloane’s case studies of disease in his natural history, Benjamin Moseley’s medical tracts, and James Grainger’s georgic poem. While these physicians sought to provide authoritative models for healing bodies and for maintaining English morals and appearance, encounters with Africans’ medical knowledge transformed their medical writing. While Sloane provided complete narratives of most of his cures, from diagnosis to recovery or death, his attempts to cure Africans depart from this model, for he resisted diagnosing African bodies, raised doubts as to whether Africans’ illnesses are real, and found that his cures were ineffective. Moseley described the history and cures for common West Indian diseases, yet his account of obeah, an Afro-Caribbean medical-religious practice, disrupted his carefully ordered categories. Finally, Grainger attempted to employ the healing powers of poetry in his “West-India” georgic, only to confront unsettling parallels between the western connections between medicine and poetry and Africans’ use of “charms.” This paper ultimately calls for new methodologies for studying the medical cultures and communications of the early Caribbean: analyzing early Caribbean medical cultures requires a methodology that attends to Afro-Caribbean knowledge and practices and to colonists’ strategies of domination, as well as to moments when African knowledge shaped not just the content but also the form of colonial writing.