Visceral leishmaniasis is a widespread and deadly disease. First-line drugs are antimonials, but amphotericin B and its lipid formulations B is used for treating visceral leishmaniasis that is unresponsive to antimony. New therapeutic approaches are being actively developed, including the following: use of drug carriers targeted specifically to the parasite location, thus reduce adverse effects of drug; use of immunomodulating drugs; evaluation of natural products; phamacokinetic studies; and drug combinations. Recent clinical trials with paromomycin and miltefosine were successful and these drugs appear to be promising for the future therapy of visceral leishmaniasis. Furthermore, identification and therapeutic evaluation of specific targets in theLeishmaniaorganism could lead to new compounds, such as antileishmanial drugs and reversal agents of drug resistance.