This article identifies and describes various epidemiological aspects in the natural transmission of Chagas disease in the Americas. It also examines the relative importance of the principal vector species in the disease's transmission and the control levels that are feasible in each instance. Estimations of the population at risk, number of infected cases, and number of chronic cases are presented. Prospects for control are discussed on the basis of past results to predict the expected results with introduced species like Triatoma infestans in the Southern Cone and Rhodnius prolixus in Central America and with the other autochthonous species in areas where they are found. Finally, the article discusses the role of other transmission mechanisms in the maintenance of endemic Chagas disease.