In animal models of myocardial infarction (MI), transplantation of various types of progenitor cells has been reported to (i) improve left ventricular (LV) function, (ii) decrease LV remodeling, (iii) limit fibrosis of noninfarcted LV regions, and (iv) in some cases, reduce infarct scar size. Moreover, in some reports these beneficial effects were present despite very low rates of long-term engraftment and transdifferentiation of transplanted cells into cardiomyocytes. In contrast, in other reports, significant numbers of transplanted cells do appear to have transdifferentiated into cardiomyocytes and vascular cells. Paracrine signals emanating from transplanted cells also appear to be very important because they protect injured cardiomyocytes and may activate endogenous cardiac progenitor cells (CPCs) to generate cardiomyocytes and vascular cells. Herein, we review evidence that transplanted bone-marrow- or cardiac-derived CPCs and/or in situ CPCs can be stimulated to propagate, differentiate, and partially replace cardiomyocytes damaged during AMI. The possibility that preexisting cardiomyocytes can be induced to reenter the cell cycle and regenerate replacement cardiomyocytes is also discussed. © 2012 Elsevier Inc.