From bone marrow transplants 5 decades ago to the most recent stem cell—derived organ transplants, regenerative medicine is increasingly recognized as an emerging core component of modern practice. In cardiovascular medicine, innovation in stem cell biology has created curative solutions for the treatment of both ischemic and nonischemic cardiomyopathy. Multiple cell-based platforms have been developed, harnessing the regenerative potential of various natural and bioengineered sources. Clinical experience from the first 1000 patients (approximately) who have received stem cell therapy worldwide indicates a favorable safety profile with modest improvement in cardiac function and structural remodeling in the setting of acute myocardial infarction or chronic heart failure. Further investigation is required before early adoption and is ongoing. Broader application in practice will require continuous scientific advances to match each patient with the most effective reparative phenotype, while ensuring optimal cell delivery, dosing, and timing of intervention. An interdisciplinary effort across the scientific and clinical community within academia, biotechnology, and government will drive the successful realization of this next generation of therapeutic agents for the “broken” heart.