Malaria is a disease caused by repeated cycles of growth of the parasite Plasmodium in the erythrocyte. Various cellular and molecular strategies allow the parasite to evade the human immune response for many cycles of parasite multiplication. Under certain circumstances Plasmodium infection causes severe anemia or cerebral malaria; the expression of disease is influenced by both parasite and host factors, as exemplified by the exacerbation of disease during pregnancy. This article provides an overview of malaria pathogenesis, synthesizing the recent field, laboratory, and epidemiological data that will lead to the development of strategies to reduce mortality and morbidity.