Despite many advances in cardiovascular medicine, heart failure (HF) remains the leading cause of death in developed countries affecting at least 10 million people in Western Europe alone. The poor long-term prognosis of HF patients, and immense public health implications has fuelled interest in finding new therapeutic modalities. Recent observations of the beneficial effect of stem cells on the damaged heart in animal experiments have generated tremendous excitement and stimulated clinical studies suggesting that this approach is feasible, safe, and potentially effective in humans. Cell-based myocardial regeneration is currently explored for a wide range of cardiac disease states, including acute and chronic ischemic myocardial damage, cardiomyopathy and as biological heart pacemakers. The aim of the present manuscript is to review the work that has been done to establish the role of stem cells in cardiac repair, give an update on the clinical trials performed so far, as well as to discuss critically the controversies, challenges and future surrounding this novel therapeutic concept.