The advent of stem cell treatment has opened new strategies in the repair of the damaged heart. Clinical observations have shown a mild mechanical improvement in the absence of significant electrophysiological abnormalities in patients treated with bone marrow stem cells. However, when skeletal myoblasts were implanted into the scarred infarcted human myocardium, serious arrhythmias occurred, requiring the implantation of pacemaker devices. Ventricular arrhythmias involve nearly 10% of patients with myocardial infarction and are responsible for a 6-fold increase in mortality. Yet, very few studies have addressed the issue of the electrophysiological effects of implantation, engraftment and differentiation of regenerating cells within the injured tissue. Moreover, little is known about the existence of a true multipotent stem cell giving rise not only to muscular and vascular structures but also to the cardiac cell system specialized in generation and conduction of electrical impulses. In addition, the changes in adrenergic and muscarinic effector/receptors pathways need to be investigated with the goal of establishing their contribution to a coordinated biological, structural and functional recovery of the infarcted myocardial tissue. Experiments by our laboratory have shown that local application of growth factors or local injection of resident cardiac stem cells may represent an effective approach to achieve a substantial myocardial improvement. Yet, several biological, anatomical and functional issues need to be resolved before the therapeutic benefits of regenerative strategies obtained in experimental animals can be safely applied in the clinical setting.