No randomized clinical trials regarding the etiological treatment of chronic Chagas disease can be found in the medical literature. However, other 'evidence' sustaining the use of anti-Trypanosoma cruzi drugs for adult individuals with Chagas disease will be analyzed along with the limitations in evaluating the treatment efficacy. Today, the hypothesis of T. cruzi persistence in the target organs giving rise to the chronic inflammatory response is sustained. In addition, several experimental, pathological, nonrandomized clinical studies and studies based on the response or serological evolution (besides the clinical experience) demonstrate the role of T. cruzi in the pathogenesis of the chronic stage and the efficacy of etiological treatment to reduce the titers of antibodies and the progression of chronic Chagas heart disease. All of this supports the recommendation of treatment for every patient diagnosed with Chagas disease. The interpretation of this sum of evidence is not considered from the perspective of evidence-based medicine.