The Leishmania donovani complex includes L. chagasi and L. infantum, and causes visceral leishmaniasis (VL), a disseminated and potentially fatal form of leishmaniasis. The treatment options for VL are limited. Pentavalent antimonials (Sbv) are the first-line treatment options worldwide except for in Europe and Sbv-unresponsive regions of India. Amphotericin B deoxycholate is the drug of choice in India, as are its lipid formulations in Europe. However, liposomal amphotericin B (AmBisome, Gilead Sciences, Inc.) is the best antileishmanial formulation, but its prohibitive cost limits its use in endemic countries. Preferential pricing of AmBisome for patients with VL may provide hope for these underprivileged patients. Oral miltefosine and paromomycin are the other drugs that have been recently developed. Limited therapeutic options, the potential for development of resistance and serious toxicity associated with antileishmanial drugs necessitates a change in the treatment policy. A shift from monotherapy to multi-drug combinations of short courses delivered at no or affordable cost, through directly observed therapy, seems to be the only way to develop the treatment of this disease.