Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi, can lead to severe cardiac and gastrointestinal disease. Most persons acquire this infection through contact with vector bugs carrying T. cruzi in endemic areas of Latin America. Infection can also be acquired by congenital, transfusion, transplantation, and foodborne transmission. Although an estimated 300,000 persons with Chagas disease live in the United States, little is known about the burden of chagasic heart disease. It is not known how often congenital or vector-borne transmission of T. cruzi occurs in the United States, although it is known that infected mothers and infected vector bugs are found in this country. Better diagnostic tests and treatment drugs are needed to improve patient care, and research is needed to define transmission risks and develop strategies to prevent new infections and reduce the burden of disease.