Cardiomyopathy is the most important clinical manifestation in the chronic phase of Chagas' disease because of its frequency, severity and impact on morbidity and mortality. The extracellular matrix degradation during cardiac remodeling in Trypanosoma cruzi infection is driven by matrix metalloproteinases (MMPs), primarily the MMP-2 and MMP-9 gelatinases. MMPs also regulate some molecules related to inflammation, such as growth factors, cytokines and chemokines. The involvement of MMP-2 and MMP-9 is not yet fully understood in Chagas' disease. It has been proposed that the gelatinases may have opposite effect on inflammation/regulation and cardiac remodeling. MMP-2 would participate in regulation, offering a protective role for cardiac damage in asymptomatic patients and would be a good marker for the initiation of changes in the heart. On the other hand, MMP-9 can be used as a marker for serious changes on the heart and would be associated with inflammation and fibrosis. Here, we consolidate all characteristics involving MMP-2 and MMP-9 in Chagas' disease based on current studies to clarify their participation on the inflammation/regulation and fibrosis, and the synergistic or antagonistic role between them.