Trypanosoma cruzi is the etiological agent of Chagas disease (CD), considered one of the most important parasitic infections in Latin America. Between 25 and 90 million humans are at infection risk via at least one of multiple infection mechanisms. Under natural conditions, the principal transmission modes are transplacental or via one of more than 140 hematophagous triatomine bugs (Reduviidae: Triatominae). Triatomines acquire the parasite from mammal reservoirs due to their obligate blood-feeding (albeit triatomines can also feed on non-reservoir vertebrates such as birds and reptiles). The disease burden for CD in the Latin America and Caribbean region, based on disability-adjusted life-years (DALYs), is at least five times greater than that of malaria, and is approximately one-fifth that of HIV/AIDS. In recent decades, CD has extended to other continents outside natural reservoir or vector distributions due to human migration, with a minimum estimated 10 million individuals infected worldwide.