Large-scale antimony resistance in the treatment of visceral leishmaniasis (VL) in north Bihar, India, has led to the development of miltefosine as an alternative therapy. In a pilot study and later in three Phase II studies involving 249 patients, oral miltefosine, 100-150 mg/day for 28 days, was shown to cure approximately 90% patients with reasonable safety. In the pivotal Phase III trial, 299 patients were treated at three centres with amphotericin B as the comparator drug (99 patients). In this trial 38% and 20% patients had mild to moderate vomiting and diarrhoea respectively, similar to previous studies. Asymptomatic transient elevation of hepatic transaminases and mild renal dysfunction were observed in 15% and 10% patients respectively. The final cure rate was 94% with miltefosine and 97% with amphotericin B; based on these results, the drug was approved in India. Subsequently in two paediatric studies involving 119 patients in the age group of 2-11 years, the safety and efficacy of miltefosine (2.5 mg/kg daily for 28 days) was established with a cure rate (94%) similar to that seen in adults. Miltefosine is the first oral antileishmanial drug with a high degree of safety and efficacy for the treatment of VL.