Cardiac cell therapy has been initially designed to regenerate the infarcted myocardium through its repopulation by new cells able to restore function of scar areas. Six years after the first human application of this novel approach, it is timely appropriate to review the results of the first randomised trials in the three major indications, i.e., acute myocardial infarction, heart failure, and refractory angina. It should be recognized that the results are mixed, with benefits ranging from absent to transient and, at most, marginal. However, lessons drawn from this first wave of clinical series and the experimental data that have been concomitantly collected are multiple and highly informative. They indicate that adult stem cells, whether muscular or bone marrow-derived, fail to generate new cardiomyocytes. They suggest that the potential benefits of cardiac cell therapy are thus mediated by alternate mechanisms such as limitation of left ventricular remodelling or paracrine activation of signalling pathways involved in angiogenesis. They highlight the fact that the therapeutic benefits of grafted cells will not be fully exploited until issues of cell transfer and postengraftment survival have not been adequately addressed. These observations thus allow us to better fine-tune upcoming research, which should specifically concentrate on the development of cells featuring a true regeneration potential. In this setting, the greatest promises are currently held by embryonic stem cells. To cite this article: P. Menasché, C. R. Biologies 330 (2007). © 2007.