Transforming growth factor-β (TGF-β) influences the development of myocardiopathy in Chagas disease through regulation of (i) parasite invasion of heart cells, (ii) an intracellular parasite cycle, (iii) inflammation and immune response, (iv) heart fibrosis and remodeling, and (v) gap junction modulation and heart conduction. In this review, we discuss the rationale for developing TGF-β signaling–interfering therapies as adjuvant approaches for the management of the cardiac alterations of Chagas disease-affected patients.2030-01-01