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We discuss here the rapid progress of stem cell therapy in myocardial infarction. In particular, we focus on the issue of transdifferentiation as a “hallmark” of the stem cell's potential to replace damaged cells of the heart. A study by Henning and colleagues in this issue of Cell Transplantation supports the alternative notion of a nontransdifferentiation-mediated protection of the heart as an equally robust mechanism underlying the therapeutic potential of stem cells.