Bioactive molecules occur in plants as secondary metabolites and as defence mechanisms against predation, herbivores, fungal attack, microbial invasion and viral infection. Throughout the world indigenous peoples have discovered plants with pharmacological activity; many useful drugs such as vincristine, reserpine, quinine, and even aspirin, have their origins in indigenous ethnopharmacologies. Three features characterize indigenous cultures that are most likely to have discovered useful natural products: (1) possession of a conservative ethnomedical tradition with established cultural mechanisms for accurate transmission of ethnopharmacological knowledge; (2) residence in an area with a diverse flora; and (3) continuity of residence in the area over many generations. Ethnopharmacological data derived from such cultures can be considered as analogues of human bioassay data. Yet indigenous ethnomedical traditions are rapidly disappearing. To preserve indigenous discoveries and make them accessible and useful to Western medicine, collaboration is required between linguistically sophisticated ethnobotanists, pharmacognosists, natural product chemists and pharmacologists. Ethnopharmacologists must be aware of all three components of indigenous medical traditions (a cosmological foundation, a repertoire of crude natural products, and a health care delivery system) to facilitate transfer of useful compounds and information to Western medicine, as well as to protect the interests and cultural integrity of indigenous peoples.