Host immune responses have a direct impact on the efficacy of chemotherapy against leishmaniasis, one of the most important of the neglected tropical diseases. Although there have been significant advances in recent years to minimize drug toxicity, cost and treatment duration, notably with the develop ment of short-course combined therapy for visceral leishmaniasis, the potential for drug resistance and a paucity of new drugs in development remain major challenges for the future. The use of immunomodulators in combination with conventional chemotherapy to enhance host immune responses may have several advantages as a means to improving current therapeutic regimens.