Treatment of ischemic heart disease with injections of bone-marrow-derived stem cells is a promising new modality. However, recent medium-sized placebo controlled trials in patients with acute myocardial infarction have not been conclusive regarding the treatment effect. This short review aims to elucidate some of the unresolved issues raised by the first clinical trials. These include long-term safety, tissue-distribution of infused cells, selecting the optimal cell type and number, timing of the treatment, and the mechanism of a potential treatment effect.