Over the past decade, cell therapy has emerged as a potential new treatment of a variety of cardiac diseases, including acute myocardial infarction, refractory angina, and chronic heart failure. A myriad of cell types have been tested experimentally, each of them being usually credited by its advocates of a high "regeneration" potential. This has led to a flurry of clinical trials entailing the use of skeletal myoblasts or bone marrow-derived cells either unfractionated or enriched in progenitor subpopulations. As often in medicine, the hype generated by the early uncontrolled and small-sized studies has been dampened by the marginally successful outcomes of the subsequent, more rigorously conducted randomized trials. Although they may have failed to achieve their primary end points, these trials have been positive in the sense that they have allowed to identify some key issues and it is reasonable to speculate that if these issues can now be addressed by appropriately focused benchwork, the outcomes of the second generation of cell-transplantation studies would likely be upgraded. It, thus, appears that not "one cell fits all" but that the selection of the cell type should be tailored to the primary clinical indication. On the one hand, it does not make sense to develop an "ideal" cell in a culture dish, if we remain unable to deliver it appropriately and to keep it alive, at least for a while, which requires to improve on the delivery techniques and to provide cells along with the vascular and extracellular matrix type of support necessary for their survival and patterning. On the other hand, the persisting mechanistic uncertainties about cell therapy should not preclude continuing clinical trials, which often provide the unique opportunity of identifying issues missed by our suboptimal preclinical models. Finally, regardless of whether cells are expected to act paracrinally or by physically replacing lost cardiomyocytes and, thus, effecting a true myocardial regeneration, safety remains a primary concern. It is, thus, important that clinical development programs be shaped in a way that allows the final cell-therapy product to be manufactured from fully traceable materials, phenotypically well characterized, consistent, scalable, sterile, and genetically stable as these characteristics are those that will be required by the ultimate gatekeeper, i.e., the regulator, and are thus unbypassable prerequisites for an effective and streamlined leap from bench to bedside.