Chagas and leishmaniasis are both neglected tropical diseases, whose inefficient therapies have made them remain the cause for millions of deaths worldwide.

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Background: Leishmaniasis, a still important public health problem, exhibits environmental risk factors such as massive migrations, urbanization, and deforestation. WHO research for Leishmaniasis has been mainly focused on the development of new tools, such as diagnostic tests, drugs, and vaccines. During the drug development strategy, only a few compounds seem promising and call for further study after the in vitro and in vivo preclinical tests. Objective: In this review, our group aimed to highlight the utmost research done during 2014 to 2019 in the fields of natural and synthetic compounds, as well as repurposed drugs and new formulations tested in vivo for Leishmania spp. Method: Based on the literature search, we used the databases MEDLINE, PUBMED, CAPES PERIODIC and ELSEVIER to delineate an interval of the last 5 years of research on each field. Results: Among the natural compounds tested, allicin and a fraction of potato tuber extract showed the most promising antileishmanial activity. Concerning synthetic compounds, quinolines, bornyl ester, thymol, benzoxaborole and nitroimidazole derivatives exhibited encouraging results. Moreover, repositioned alternatives involved combinations with known drugs and monotherapy protocols as well. In these years, new formulations were widely assessed as drug delivery systems, such as nanoparticles, micelles and liposomes in polymer conjugations. Conclusion: Drug repurposing and new formulations of already-known drugs are worthwhile approaches to promptly introduce new treatment schemes to Leishmaniasis. Nevertheless, the interest in new synthetic compounds and new formulations brings light to new treatment proposals and are notable lines of research.