Malaria has had a greater impact on world history than any other infectious disease. More than 300 to 500 million individuals worldwide are infected with Plasmodium spp, and 1.5 to 2.7 million people a year, most of whom are children, die from the infection. Malaria is endemic in over 90 countries in which 2400 million people live; this represents 40% of the world’s population. Approximately 90% of malaria deaths occur in Africa. Despite continuing efforts in vaccine development, malaria prevention is difficult, and no drug is universally effective. This article examines malaria caused by the 4 most common Plasmodium spp that infect humans, P vivax, P ovale, P malariae, and P falciparum, as well as mixed infections and the simian parasite P knowlesi. A comprehensive review of the microbiology, clinical presentation, pathogenesis, diagnosis, and treatment of these forms of malaria is given.