Severe myocardial infarction can lead to ventricular remodelling and progressive contractile dysfunction with inability of the heart to maintain perfusion to vital organs. Pharmacological and surgical interventions can only alleviate symptoms or retard further disease progression. However, these interventions fail to regenerate dead myocardium. Stem cells have the potential to replace or repair dead or injured cells after myocardial infarction. Stem cells are either integrated by themselves or provide a platform to transmit molecular signals to a target tissue without actually integrating into the tissue itself. Clinical studies, still in early stages, have reported that this therapeutic modality may lead to an overall improvement of cardiac function. Endogenous cell homing presents a promising approach that may represent an effective alternative to stem cell transplantation. Identifying factors and adequate regulation of signalling between bone marrow, peripheral circulation and infarcted myocardium are important in orchestrating the process of mobilization, incorporation, survival, differentiation and proliferation of stem cells. Moreover, the potential for magnifying stem cell-mediated paracrine effects using "genetically engineered", "preconditioned", "targeted" or "combined stem cell therapies" can provide promising options for enhancing stem cell therapy success while limiting adverse effects. It is hoped that these experimental trials will be eventually translated into successful treatment strategies in the clinical field.