The seminal experiments showing that cells transplanted in infarcted hearts could effect myocardial tissue repair have provided the proof of concept that cell therapy might be an effective means of improving the outcome of patients with severe heart failure. Because of their appealing characteristics (autologous origin, in vitro scalability, high resistance to ischemia), skeletal myoblasts have undergone extensive preclinical testing that has consistently demonstrated their ability to preserve postinfarct left ventricular function and to limit remodelling. As this functional efficacy occurs despite a poor long-term engraftment rate and the inability of myoblasts to convert into cardiomyocytes, the hypothesis has been raised that the predominant mechanism of action could involve paracrine signalling rather than a direct contractile effect of the graft. These preclinical data have paved the way for the early human trials which have confirmed the feasibility and safety of this approach. The mixed results in terms of efficacy should not be discouraging; they only reflect that the field is still in infancy and have yet been helpful in identifying some key issues like the limited efficiency of current cell transfer techniques and the high rate of early posttransplantation cell death. It is clear, however, that myoblasts and, more generally, adult stem cells cannot truly repair infarcted myocardium through the generation of new cardiomyocytes. This first wave of clinical studies thus delineates the research pathways that need to be followed for overcoming these hurdles and consequently allow myoblast transplantation to become a potentially effective adjunct to current heart failure therapies. © 2007 Elsevier Inc. All rights reserved.