Stem cell transplantation is currently generating a significant interest for use in the future treatment of cardiovascular diseases. Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical trials as bone marrow stem cells did not show significant improvement in cardiac function following transplantation. Experimental stem cell studies raised the question on the true differentiation of tissue-specific cell types following transplantation. In fact, recent studies suggest that improved cardiac function is associated with inhibition of apoptosis and fibrosis provided by factors released from stem cells following transplantation. In this review, we will discuss the effects of transplanted stem cells on engraftment and differentiation as well as factors released from stem cells on apoptosis and cardiac remodeling.