Parasites of the genus Leishmania induce a complex variety of responses in their mammalian hosts, effected and/or modulated by the immune system. The outcome of leishmanial infection of macrophages depends on factors particular to each host-parasite combination, involving not only intrinsic properties of the parasite, but also genetically determined characteristics of the host cell or of its interactions with immunocompetent cells. Following a review of evidence supporting these concepts, they are applied in describing the clinical and immunopathological spectrum of the disease as it occurs in man, with emphasis on the cutaneous and mucocutaneous leishmaniases of the Old and New World. Based on results obtained in experimental models of cutaneous leishmaniasis which reproduce features of healing and non-healing human disease, the author presents a schematic analysis of the evolution of the histopathological features of leishmanial lesions.