Leishmaniasis, in its variety of visceral (VL), cut aneous (CL) and mucocutaneous (MCL) forms, a vector-borne parasitic disease, is caused by the infection with the obligate intracellular protozoan parasite, Leishmania, transmitted by abou t 30 species of Phlebotomine sandflies. The control of leishmaniasis remains a problem–principa lly a zoonotic infection, except in epidemics where it is anthroponotic, interruption of transmis sion is difficult, though not impossible. No vaccines exist for VL, CL or MCL and chemotherapy i s inadequate and expensive. Current regimes use pentavalent antimony as primary therapy , which must be administered parenterally. Should this fail, a number of other drugs may be em ployed, depending upon the species of Leishmania concerned and the resources available to the health professionals involved. The most widely used of these is amphotericin B, which is highly active but has extensive toxicity complications. Pentamidine and Paromomycin are used in some instances, and a new anti- leishmanial, Miltefosine, may be used in the future . In short, there remains a pressing need for new anti-leishmanials and this chapter reviews the current status of chemotherapy, the various Novel Targets and some important lead compounds in antileishmanial chemotherapy.