Growing antimony resistance in patients with visceral leishmaniasis (VL) over last two decades, especially in Indian subcontinent, renders this cheap and easily available drug useless for a vast majority of patients. Use of the second line drug pentamidine isethionate, a toxic drug with declining efficacy, has largely been abandoned. Thus, in these areas amphotericin B remains the only drug; although it cures > 97% patients, infusion-related adverse events are common and occasionally serious toxicity, such as myocarditis, or death can occur. In recent years India has been the center for clinical development of new anti-leishmanial drugs like lipid formulations of amphotericin B, new drugs like parenterally administered aminosidine and oral miltefosine. The alkyl phospholipid compound miltefosine is the first effective oral compound for VL and is likely to be marketed soon. In addition to the monotherapy, efforts in development of combination chemotherapy are needed if the menace of drug resistance is to be contained.