The present article seeks to fill a number of lacunae with regard to the study of the circulation and assimilation of different bodies of medical knowledge in an important cultural contact zone, that is the Upper Guinea Coast. Building upon ongoing research on trade and cultural brokerage in the area, it focuses upon shifting attitudes and practices with regard to health and healing as a result of cultural interaction and hybridisation against the background of growing intra-African and Afro-Atlantic interaction from the fifteenth to the late seventeenth century. Largely based upon travel accounts, missionary reports and documents produced by the Portuguese Inquisition, it shows how forms of medical knowledge shifted and circulated between littoral areas and their hinterland, as well as between the coast, the Atlantic and beyond. It shows that the changing patterns of trade, migration and settlement associated with Mandé influence and Afro-Atlantic exchange had a decisive impact on changing notions of illness and therapeutic trajectories. Over the centuries, cross-cultural, reciprocal borrowing contributed to the development of healing kits employed by Africans and non-African outsiders alike, which were used and brokered by local communities in different locations in the region.