Leishmaniasis, in its variety of visceral (VL), cutaneous (CL) and mucocutaneous (MCL) forms, directly affects about 2 million people per annum, with approximately 350 million individuals at risk worldwide. During the last 10 years there have been extensive epidemics of the visceral form of the disease, which is also emerging as an important opportunistic infection in immunocompromised patients, especially those co-infected with HIV. The control of leishmaniasis remains a problem principally a zoonotic infection, except in epidemics where it is anthroponotic, interruption of transmission is difficult, though not impossible. No vaccines exist for either VL, CL or MCL and chemotherapy is 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 employed, depending upon the species of Leishmania concerned and the resources available to the health professionals involved. Recommended secondary treatment employs a variety of drugs, again depending on the nature of the infection. The most widely used of these is amphotericin B, which is highly active but has extensive toxicity complications. The newer formulations of this drug are too expensive to use for the majority of endemic countries. 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 avenues being investigated by researchers and their potential application in the future.