There is a growing interest in the clinical application for stem cell as a novel therapy for treatment of acute myocardial infarction and chronic myocardial ischaemia. The initial premise is the transplanted exogenous stem cells can engraft and integrate with host myocardium for cardiac regeneration. However, recent experimental studies suggest that multiple mechanisms, including remodelling of extracellular matrix, enhancement of neovascularisation and recruitment of endogenous stem cells are more likely to contribute to the beneficial effects of stem cell therapy that direct trans-differentiation of stem cells into functional myocardium. Among different potential cell sources, bone marrow-derived cells and skeletal myoblasts have been tested in pilot clinical trials. Phase I/II randomised controlled clinical trials suggest that intracoronary or intramyocardial injection of bone marrow-derived cells may be safe and feasible strategies for treatment of acute myocardial infarction as well as chronic myocardial ischaemia. In addition, these studies show a modest, but significant improvement in left ventricular ejection fraction and clinical status of patients after cell transplantation. Nevertheless, most of these studies included a relatively small sample size (<200) and short duration of follow-up (<6 months), and the clinical efficacy of stem cell therapy need to be confirmed by future clinical trials. Furthermore, the optimal timing, cell types and mode of delivery need to be addressed, and strategies to improve cell survival and engraftment should also be developed to overcome the potential hurdles related to cell-based therapy.