The potential for endogenous or supplementary stem cells to restore the form and function of damaged tissues is particularly promising for overcoming the restricted regenerative capacity of the mammalian heart. To maintain blood circulation, this essential organ needs to launch a rapid response to repair damage of the muscle wall and to prevent muscle loss. The capacity of growth factors to supplement the repair process has been successfully applied to restore the integrity of damaged skeletal muscle, reducing the fibrotic response to injury, and recruiting local populations of self-renewing precursor cells and circulating stem cells. We review the recent evidence that extension of growth factor supplementation to the heart may overcome its inherent regenerative impediments through improvement of the local tissue environment and stimulation of cell replacement, and we speculate on future research directions for treatment of myocardial damage.