The chemotherapy currently available for leishmaniasis is far from satisfactory. Resistance to the pentavalent antimonials, which have been the recommended drugs for the treatment of both visceral (VL) and cutaneous leishmaniasis (CL) for >50 years, is now widespread in India. Although new drugs have become available in recent years for the treatment of VL, including AmBisome((R)), the excellent but highly expensive liposomal formulation of amphotericin B, and the oral drug miltefosine, which has now been registered in India, treatment problems remain. Parenteral and topical formulations of the aminoglycoside paromomycin offer potential treatments for VL and CL, respectively. The search for new drugs continues, with bisphosphonates, for example, risedronate and pamidronate, and plant derivatives such as licochalcone A and quinoline alkaloids being reported to have activity against experimental animal infections. The immunomodulator imiquimod has proved to be an adjunct for CL therapy. Many potential drug targets have been identified in biochemical and molecular studies, and some have been validated. Attempts to exploit these targets are in progress.