Findings in the cardiology field from the last three decades of the 20th century were ruled by the theory that the heart is a post-mitotic organ, incapable to regenerate. Recent studies have brought evidences regarding the existence of some cells residing in the adult heart, having stem properties. These cardiac stem cells (CSCs) govern myocardial homeostasis and repair by differentiating into new cardiomyocytes, smooth muscle cells and vascular endothelial cells and also by releasing proangiogenic and procardiogenic cytokines. Hence, CSC-based therapy seems to be a promising tool for repairing failing hearts. This review presents the current data regarding various subpopulations of CSCs and their regenerative potential revealed by phase I clinical trials; finally, future perspectives for the development of more advanced therapeutic protocols are proposed.