Beginning as a silvatic enzoosis involving Trypanosoma cruzi and a range of small mammals and marsupials, human Chagas disease probably emerged as a sparse focal disease at different points in the Americas well before the Christian period. Subsequently spread through internal population migrations, the disease would have become more widespread where the insect vectors became associated with rural settlements. It appears to have spread most widely during the post-Colombian period, especially from the mid 19th to mid 20th centuries when the human infection appears to have peaked in incidence and prevalence. In historical terms, there are sparse indications of probable acute cases, chronic cardiopathy, and megacolon, but such conditions are difficult to diagnose accurately. In contrast, megaoesophagus seems a more specific marker of chronic Chagas disease, with a number of reports of its occurrence in various parts of Brazil, especially since the 18th century. The main impact of chronic Chagas disease corresponds primarily to the occurrence of chronic chagasic cardiopathy, and recognition and characterization of this has been the main stimulus for large-scale control interventions in the endemic countries since the 1950s.