A recent upsurge of malaria in endemic-disease areas with explosive epidemics in many parts of Africa is probably caused by many factors, including rapidly spreading resistance to antimalarial drugs, climatic changes, and population movements. In Africa, malaria is caused by Plasmodium falciparum and is transmitted by Anopheles gambiae complex. Control efforts have been piecemeal and not coordinated. Strategies for control should have a solid research base both for developing antimalarial drugs and vaccines and for better understanding the pathogenesis, vector dynamics, epidemiology, and socioeconomic aspects of the disease. An international collaborative approach is needed to build appropriate research in a national context and to effectively translate research results into practical applications in the field. The Multilateral Initiative for Malaria in Africa can combine all of the above strategies to plan and coordinate partnerships, networking, and innovative approaches between African scientists and their Northern partners.