This chapter provides information on host response to leishmania infection. Leishmaniasis is caused by the infection with protozoan parasites of the genus Leishmania. It is not a single disease but constitutes a variety of syndromes ranging from local, self-healing skin ulcers (cutaneous leishmaniasis) to a severe and life-threatening systemic disease, diagnosed by direct demonstration of the parasites (microscopy, culture, DNA, or RNA analysis) in appropriately selected material (skin, spleen, bone marrow, other suspected sites) and/or by immunodiagnosis. Persistence of Leishmania is also found after clinical cure of human infections. By PCR technique and in vitro culture, parasites are also detected in the scars of 50% of the patients with treated and healed L. (Viannia) braziliensis infection between 5 and 11 years after successful therapy. These data suggest that, once infected, the mammalian host probably harbors the parasites life-long. Prevention of parasite replication above a certain threshold and thereby preventing exacerbation of the disease is an active process.