Members of the genus Leishmania are important intracellular pathogens that produce either cutaneous, mucocutaneous, or visceral disease in many areas of the world. In humans as well as in other mammals, the parasite is inoculated through the skin as a flagellated, extracellular promastigote by its arthropod vector, the sandfly. Once in its mammalian host, the promastigote converts to its amastigote stage, which lacks an exteriorized flagellum and is found solely within mononuclear phagocytes during established infection. In vitro, human monocyte-derived macrophages and peritoneal macrophages from several species of rodents can ingest both promastigotes and amastigotes, and they can permit intracellular multiplication of amastigotes only. Although serum factors may play a role in the pathogenesis of the disease and in protection against reinfection, the resolution of leishmaniasis is dependent primarily on cell-mediated immune responses. There appears to be a complicated interplay between cell-mediated helper and suppressor activities. The outcome of infection in each type of leishmaniasis depends on the complex and intriguing interaction of virulence factors inherent in the parasite and genetically determined host defense mechanisms.