The lack of myocardial repair after myocardial infarction and the heart failure that eventually ensues was thought of as proof that myocardial cell regeneration and myocardial repair mechanisms do not exist. Recently, growing experimental and clinical evidence has proven this concept wrong. Cardiac stem cells and endogenous myocardial repair mechanisms do exist; however, they do not produce significant myocardial repair. Similarly, the preliminary results of stem cell therapy for myocardial repair have shown early promise but modest results. Preclinical studies are the key to understanding stem cell senescence and lack of cellular contact and vasculature in the infarcted region. Additional laboratory studies are sure to unlock the therapeutic mechanisms that will be required for significant myocardial repair.