Trypanosoma cruzi is a blooded-flagellated protozoan transmitted to humans either by blood-sucking triatomine vectors, by blood transfusion or by congenital transmission causing the Chagas’ disease or American Trypanosomiasis. Serologic testing for specific antibodies to T. cruzi antigens is the most common employed approach for diagnosing chronic infection with this protozoan parasite in clinical patients as well as in blood donors. No assay has been universally accepted as the gold standard for the serologic diagnosis of T. cruzi infection, and likewise no assay is viewed as a definitive confirmatory test. Therefore, the antigen fractions (antigenic extract form, recombinant antigens and/or synthetic peptides) may have different affinities for both specific and non-specific antibodies and can produce variable sensitivities. To date, excreted-secreted antigens by the parasites have been proposed as antigen fractions for the detection of this parasite: Trypomastigote Excretory-Secretory Antigens (TESA), composed mainly of surface components such as SAPA, Gala1-3Gal, Tc-85 and T-DAF epitopes and excreted dismutase (SODe) appears to provide good sensitivity and specificity as reagents for the diagnosis of Chagas’ disease. This chapter revises the research on excreted/secreted antigens and their utility to establish an ideal diagnostic confirmatory Chagas test.