Many clinical studies have been conducted with different cell types: skeletal myoblasts (SM), bone marrow‐derived mononuclear cells (BM‐MNC), mesenchymal stromal cells (MSC), and resident cardiac stem cells (CSC), to name a few . ...the study did not achieve its primary endpoint, which was the improvement in left ventricular ejection fraction (LVEF). ...concerns were expressed regarding a potential pro‐arrhythmic effect played by SM therapy, likely due to the lack of electrical coupling. The first study was a phase I clinical trial investigating the feasibility and safety of autologous SM transplant in patients affected by ischemic heart disease undergoing left ventricular assist device (LVAD) implantation as a bridge to orthotopic heart transplantation. Overall, the take‐home messages of these studies are (a) SM are capable of permanently engrafting in the human heart, even though the percentage of cells surviving is extremely low, (b) SM fail to transdifferentiate into mature cardiomyocytes, (c) SM fail in forming electro‐mechanical couplings with native cardiomyocytes and do not integrate with the rest of the contracting cardiac mass, and (d) the positive effects reported by the MAGIC and other clinical trials in terms of ventricular remodeling and revascularization are very likely mediated by paracrine effects.