For the last decade chloroquine-resistant Plasmodium falciparum (CRPF) has spread explosively in sub-Saharan Africa. In some areas of the continent, CRPF is so intense that chloroquine can hardly be said to have any efficacy. There is emerging evidence that CRPF is linked with increased incidence of mortality, severe disease and emergence of epidemics. Whereas the normal response to this trend of events would be replacing chloroquine with another effective drug, such a decision is hampered by the limited number of antimalarials currently available. There is a fear that changing too early would lead to depletion of available drugs. Yet a delay may be costly and catastrophic. Since the development of new antimalarials is deemed commercially unviable by high-income countries, there is need for a pan-African project aimed at the development of new antimalarials. Such a project could be jointly funded from African governments and the donor community under the coordination of either the World Health Organization or the Organization of African Unity. To delay the emergence and spread of resistance by P. falciparum to new and old drugs, there is need for: improving rational drugs use; limiting mass use of drugs as in chemoprophylaxis and in medicated salt; and increasing the use of impregnated bed nets.