This chapter focuses on recent advances in preclinical and clinical research of visceral and cutaneous leishmaniasis. It discusses the roles of humoral and cell-mediated immunity, and cytokines such as interferon gamma, in understanding the mechanism of action of the anti-leishmanial immune response. The life cycle of Leishmania within the sandfly vector includes amastigote, multiple promastigote, and paramastigote stages and is reviewed by Alexander and Russell. The clinical features are associated with release of amastigotes from phagocytic cells and dissemination to the reticuloendothelial cells of the skin, bone marrow, liver, spleen, and lymph nodes. The microbicidal macrophage activity initially associated with Leishmania killing was the production of reactive oxygen intermediates via the respiratoryburst. Promastigotes have been shown to stimulate respiratory burst activity far more effectively than amastigotes. The ability to study mechanisms of pathogenicity and immune response in Leishmania infections has been greatly facilitated by the availability of animal models which closely resemble the human infection.