Experimental studies suggest that cardiac transfer of stem and progenitor cells can have a favorable impact on tissue perfusion and contractile performance after acute myocardial infarction (AMI). While the mechanistic background of stem cell therapy is still intensely debated, the concept of cell therapy has already been introduced into the clinical setting, where small, mostly uncontrolled trials indicate that stem cell therapy may be feasible in patients. The overall clinical experience also suggests that stem cell therapy can be safely performed, if the right cell type is used in the right clinical setting. Preliminary efficacy data indicate that stem cells have the potential to enhance myocardial perfusion and/or contractile performance in patients with AMI. The field now is rapidly moving towards intermediate-size, double-blinded trials to gather more safety and efficacy data. Ultimately, large outcome trials will have to be conducted. At the same time, continued basic research to elucidate the underlying mechanism of stem cell therapy is needed.