Trypanosoma cruzi (T. cruzi) infection is endemic in Latin America and is becoming a worldwide health burden. It may lead to heterogeneous phenotypes. Early diagnosis of T. cruzi infection is crucial. Several biomarkers have been reported in Chagas heart disease (ChHD), but most are nonspecific for T. cruzi infection. Prognosis of ChHD patients is worse compared with other etiologies, with sudden cardiac death as an important mode of death. Most ChHD patients display diffuse myocarditis with fibrosis and hypertrophy. The remodeling process seems to be associated with etiopathogenic mechanisms and neurohormonal activation. Pharmacological treatment and antiarrhythmic therapy for ChHD is mostly based on results for other etiologies. Heart transplantation is an established, valuable therapeutic option in refractory ChHD. Implantable cardioverter-defibrillators are indicated for prevention of secondary sudden cardiac death. Specific etiological treatments should be revisited and reserved for select patients. Understanding and management of ChHD need improvement, including development of randomized trials.