An effective treatment for Trypanosoma cruzi infection has been investigated, since the 30s. The goals of the specific treatment against T. cruzi infection are, at the individual level, to eliminate the parasite, and to reduce the probability of developing Chagas disease. At the end of the 60s and at the beginning of the 70s, two compounds were clinically investigated in Argentina: Nifurtimox and Benznidazole. After the approval by the Ministry of Health, in 1983 the first guidelines for the treatment of T. cruzi infection were proposed and approved. These guidelines recommended the treatment of cases in the acute phase. Due to the publication of new information in support of the utility of these drugs for treating cases in the indeterminate phase of Chagas disease, in 1997 the original guidelines were revised and new procedures were approved. At present, the treatment is recommended for: 1) all patients undergoing the acute phase; 2) children and young people undergoing the indeterminate phase; 3) adult patients undergoing the indeterminate phase or with incipient heart lesions; 4) laboratory accidents and during surgery, and 5) organ transplant recipients or donors. The general clinical laboratory control is needed for the intra-treatment monitoring of the patient. Titration of specific antibodies with monospecific antigens has been shown to be an adequate marker of therapeutic efficacy.