Recent data indicate that the heart is a self-renewing organ and contains a pool of progenitor cells (PCs). According to the new paradigm, this resident population of multipotent undifferentiated cells gives rise to myocytes, endothelial cells, smooth muscle cells and fibroblasts. Understanding the function of cardiac PCs is critical for the implementation of these cells in the treatment of the diseased human heart. However, cardiac repair is an extremely complex phenomenon. Efficient myocardial regeneration requires restoration of segmental and focal areas of myocardial scarring, replacement of damaged coronary arteries, arterioles and capillaries, and substitution of hypertrophied poorly contracting myocytes with smaller better functioning parenchymal cells. To achieve these goals, the acquisition of a more profound knowledge of the biology of cardiac PCs cells and their fate following pathologic insults represents an essential need.