The Southern Cone Initiative (Iniciativa de Salud del Cono Sur, INCOSUR) to control domestic transmission of Trypanosoma cruzi is a substantial achievement based on the enthusiasm of the scientific community, effective strategies, leadership, and cost-effectiveness. INCOSUR triggered the launch of other regional initiatives in Central America and in the Andean and Amazon regions, which have all made progress. The Central American Initiative targeted the elimination of an imported triatomine bug (Rhodnius prolixus) and the control of a widespread native species (Triatoma dimidiata), and faced constraints such as a small scientific community, the difficulty in controlling a native species, and a vector control programme that had fragmented under a decentralized health system. International organizations such as the Japan International Cooperation Agency (JICA) have played an important role in bridging the gaps between fragmented organizational resources. Guatemala achieved virtual elimination of R. prolixus and ;reduction of Tri. Dimidiata and El Salvador and Honduras revitalized their national programmes. The programme also revealed new challenges. Tri. dimidiata control needs to cover a large geographic area efficiently with stratification, quality control, community mobilization, and information management. Stakeholders such as the National Chagas Program, the local health system and their communities, as well as local government must share responsibilities to continue comprehensive vector control.