The ancestor of Trypanosome cruzi was probably introduced to South American via bats approximately 7-10 million years ago. When the first humans arrived in the New World, a sylvatic cycle of Chagas disease was then already well established. Paleoparasitological data suggests that human American trypanosomiasis originated in the Andean area when people founded the first settlements in the coastal region of the Atacama Desert. Identification of T. cruzi as the etiological agent and triatome bugs as the transmission vector of Chagas disease occurred within a few years at the beginning of the 20 century. History also teaches us that human activity leading to environmental changes, in particular deforestation, is the main cause for the spread of Chagas disease. Recently, migration of T. cruzi-infected patients has led to a distribution of Chagas disease from Latin America to non-endemic countries in Europe, North America and western Pacific region.