Each year, up to three million deaths due to malaria and close to five billion episodes of clinical illness possibly meriting antimalarial therapy occur throughout the world, with Africa having more than 90% of this burden. Almost 3% of disability adjusted life years are due to malaria mortality globally, 10% in Africa. New information is presented in this supplement on malaria-related perinatal mortality, occurrence of human immunodeficiency virus in pregnancy, undernutrition, and neurologic, cognitive, and developmental sequelae. The entomologic determinants of transmission and uses of modeling for program planning and disease prediction and prevention are discussed. New data are presented from the Democratic Republic of the Congo, Tanzania, Ethiopia, and Zimbabwe on the increasing urban malaria problem and on epidemic malaria. Between 6% and 28% of the malaria burden may occur in cities, which comprise less than 2% of the African surface. Macroeconomic projections show that the costs are far greater than the costs of individual cases, with a substantial deleterious impact of malaria on schooling of patients, external investments into endemic countries, and tourism. Poor populations are at greatest risk; 58% of the cases occur in the poorest 20% of the world's population and these patients receive the worst care and have catastrophic economic consequences from their illness. This social vulnerability requires better understanding for improving deployment, access, quality, and use of effective interventions. Studies from Ghana and elsewhere indicate that for every patient with febrile illness assumed to be malaria seen in health facilities, 4-5 episodes occur in the community. Effective actions for malaria control mandate rational public policies; market forces, which often drive sales and use of drugs and other interventions, are unlikely to guarantee their use. Artemisinin-based combination therapy (ACT) for malaria is rapidly gaining acceptance as an effective approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20-2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs. The burden of malaria in one district in Tanzania has not decreased since the primary health care approach replaced the vertical malaria control efforts of the 1960s. Despite decentralization, this situation resulted, in part, from weak district management capacity, poor coordination, inadequate monitoring, and lack of training of key staff. Experience in the Solomon Islands showed that spraying with DDT, use of insecticide-treated bed nets (ITNs), and health education were all associated with disease reduction. The use of nets permitted a reduction in DDT spraying, but could not replace it without an increased malaria incidence. Baseli...