It is in the "Old Europe" that cellular transplantation for heart disease has entered the clinical arena when, on June 15, 2000, we performed the first intramyocardial transplantation of autologous skeletal myoblasts in a 75-year old patient suffering from severe ischemic left ventricular dysfunction. Two weeks before, he had undergone a muscular biopsy at the thigh. Expansion of this tissue specimen in a dedicated medium and according to customized GMP-compliant procedures yielded a total of 800 × 106 cells, of which 65% were CD-56-positive myoblasts. These cells were then implanted in multiple sites in the core and at the borders of a postinfarction posterior nonviable scar while 2 bypass grafts were placed on the left anterior descending and diagonal coronary arteries under conventional cardiopulmonary bypass. The postoperative course was uneventful. The patient's condition subsequently improved and repeat echocardiograms documented the clear restoration of some systolic thickening in the once akinetic area. This patient died 18 months after the operation from a stroke and autopsy provided evidence for the reality of cell engraftment under the form of scar-embedded clusters of myotubes, featuring typical cross-striations and aligned parallel to the host cardiomyocytes. This case initiated a phase I trial primarily designed to assess the feasibility and safety of the procedure and ultimately included 10 patients. Since then, 4 additional studies of myoblast transplantation have been reported in Europe, of which two entailed surgical implantations. The two others used catheters for cell delivery and only one has been published at the time of this writing. The purpose of this chapter is to critically summarize the main lessons gained from these early trials, to highlight the issues that remain to be addressed and to place myoblasts in the more general perspective of cell transplantation for repair of chronically infarcted myocardium. © 2006 Springer Science+Business Media, Inc.