 The global increase in treatment failure for old and new world leishmaniasis is due to drug resistance, which is influenced by the HIV-AIDS epidemic and other factors. Pentavalent antimonials have been used successfully worldwide for leishmaniasis treatment, but resistance has increased in North Bihar, India. This review discusses the molecular epidemiology of resistance related to leishmania donovani, its impact on drug combination therapies, and the molecular mechanisms contributing to resistance to antimonials, amphotericin B, and mitfosin. This article was authored by Alisha Pontesuka, Francisco Gamarro, Jean-Claude Dujardin, and others.