We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericinB) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fi ll in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.