The deployment of antiprotozoal drugs on a large scale for prophylaxis or monotherapy inevitably results in the selection of drug-resistance. The use of appropriately selected drug combinations may impede this process. Point mutations underlie resistance to dihydrofolate reductase inhibitors such as pyrimethamine. Potentiating combinations of such compounds with sulfonamides or sulfones have effectively delayed resistance to them. The use of triple combinations may be of value in protecting such compounds as chloroquine and mefloquine, resistance to which is associated in some cases with gene amplification. It is essential to seek partner compounds for any new antimalarials, e.g. artemisinin. Past experience with existing compounds is discussed and the need to make use of all available means of interrupting malaria transmission is stressed, rather than depending entirely on drugs.