BACKGROUND: New World leishmaniasis is an important endemic disease and public health problem in developing countries. The increase in ecologic tourism has extended this problem to developed countries. Few drugs have emerged over the past 50 years, and drug resistance has increased, such that the cure rate is no better than 80% in large studies. Despite these data, there has been no systematic review with a meta-analysis of the therapy used in this important tropical disease. The aim of this study was to determine the best drug management in the treatment of cutaneous leishmaniasis (CL) in Latin America based on the best studies published in the medical literature. METHODS: MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to CL and therapy. Articles with adequate data on cure and treatment failure, internal and external validity information, and more than four patients in each treatment arm were included. RESULTS: Fifty-four articles met our inclusion criteria and 12 were included in the meta-analysis. Pentavalent antimonials were the most studied drugs, with a total of 1150 patients, achieving a cure rate of 76.5%. The cure rate of pentamidine was similar to that of pentavalent antimonials. Other drugs showed variable results, and all demonstrated an inferior response. CONCLUSION: Although pentavalent antimonials are the drugs of choice in the treatment of CL, pentamidine showed similar results. Nevertheless, several aspects, such as cost, adverse effects, local experience, and availability of drugs to treat CL, must be considered when determining the best management of this disease, especially in developing countries where resources are scarce.