Publisher Summary Chagas' disease is a trypanosomiasis caused by Trypanosoma cruzi (T. cruzi), occurring almost exclusively in Latin America. The immunopathologic theory is the one most broadly accepted as the cause of these lesions. The heart and the gastrointestinal tract are the most prominently involved structures, but the disease also involves other organs, such as the urinary tract, the eyes, and the bronchial tree. There are three relevant routes of transmission: through the vector, through transfusions, and from mother to child. Although vectors are the most important route in Latin America, transfusions are the main source of infection in countries—such as the United States and Canada—because of the high immigration rate from endemic regions. Therapy includes specific antiparasitic treatment only at the acute stage. The finding of evidence of trypanosomes in tissue has currently posed the need for drugs at the chronic stage, especially at the early stages when the anatomic changes are initially seen clinically.