© 2004 by Taylor and Francis Group, LLC. INTRODUCTION Over the past decade, cellular transplantation has progressively emerged as a potential new means of repairing infarcted myocardium, particularly in patients who have already exhausted the currently available medical, interventional, and surgical treatment options. The underlying concept is that replacement of irreversibly damaged muscle by new contractile cells should restore functionality in these necrotic areas and subsequently contribute to improvement of global heart function. Because the regenerative capacity of the adult mammalian heart [1,2] is by far too limited to compensate for the loss of cardiac cells resulting from a large infarct, and although attempts at converting the infarcted myocardium into contractile tissue by direct injection of viral vectors encoding the muscle-specific Myo-D master gene have been rather disappointing , the most clinically relevant approach is considered to be the direct transplantation of exogenously supplied cells. After extensive laboratory work, early clinical trials of surgical autologous skeletal myoblast transplantation was initiated in June, 2000 in heart failure patients , and rapidly followed by catheter-based intracoronary delivery of bone marrow-derived stem cells in the setting of acute myocardial infarction [5,6]. These phase I studies have primarily established the feasibility and safety of this novel approach and efficacy remains to be validated by prospective trials, which are under way or in preparation. In parallel, a large amount of experimental work is still mandatory to address some basic issues, particularly those pertaining to the choice of the optimal cell type, the technique most appropriate for intramyocardial cell transfer, and the adjunctive strategies required for optimizing postengraftment cell survival. The chapter will concentrate on these issues before highlighting the major lessons gained from the preliminary clinical trials.