Leishmaniasis is a protozoan vector borne disease prevalent throughout the world and present in at least 88 countries. The parasite is transmitted by infected phlebotomine sandfly bites. While conventional therapies i.e. pentavalent antimonials, amphotericin B and pentamidine continue to play a major role, it is evident that new drugs or strategies must circumvent the limitations, such as a long-term parenteral administration, toxicity, the high cost in endemic countries and the emergence of resistance, that prevail. One of the most promising drugs is miltefosine, a new oral, approved alkylphospholipid for visceral leishmaniasis with only slight adverse effects. Although we have now this recent and encouraging advance, there is still a need to develop safe, efficient and affordable new treatments for the different clinical forms that exist. This review summarises conventional therapy and the current efforts in the discovery of drugs to treat leishmaniasis with the emphasis on drug combinations to enhance efficiency and prevent the emergence of resistance, the investigation of natural products with the objective of offering new bioactive chemical structures and the development of novel antileishmanial targets.