For decades, it has been widely accepted that the heart is a terminally differentiated organ that is unable to regenerate. Studies of recipients of hearts donated by other humans have shed light on the regenerative potential of the human heart. Investigators have been able to trace the Y chromosome by fluorescence in situ hybridization or polymerase chain reaction, or both, in sex-mismatched heart recipients. Cardiac chimerism has been reported, with concentrations of chimeric cells ranging from 0.04% to 10.0%. Cardiac chimerism after bone marrow or progenitor cell transplantation has also been reported to a low extent (approximately 0.20%), suggesting that a fraction of the extracardiac cells that colonize the myocardium are of bone marrow origin. Cardiac chimerism after pregnancy with male offspring (fetal cell microchimerism) has also been demonstrated. Cells of fetal origin have been shown to be capable of differentiating into myocardial cells. Collectively, we show that chimerism studies provide a proof of concept of a process that it is likely to be part of normal cardiac homeostasis in humans but apparently insufficient for cardiac repair in diseased hearts.