Chagas disease, discovered over a century ago, continues to pose a global health challenge, affecting millions mainly in Latin America. This historical review with commentary outlines the disease’s discovery, its evolution into a global concern due to migration, and highlights significant advances in diagnostics and treatment strategies. Despite these advancements, the paper discusses ongoing challenges in eradication, including vector control, congenital transmission, the disease’s asymptomatic nature, and socioeconomic barriers to effective management. It calls for a multidisciplinary approach, enhanced diagnostics, improved treatment accessibility, and sustained vector control efforts. The review emphasizes the importance of global collaboration and increased funding to reduce Chagas disease’s impact.