The recent establishment of the human embryonic stem cell lines and the demonstration of their ability to differentiate in vitro to cardiomyocytes brings a unique promise to both basic and clinical research. The present report describes the characteristics of the human embryonic stem cell lines and focuses on the structural and functional properties of their cardiomyocyte derivatives. In addition, the possible signals and cues involved in the commitment and early differentiation of cardiomyocytes will be discussed. Finally, the potential applications of this unique differentiating system in several research and clinical areas are discussed, with special emphasis on the steps required to fully harness their potential for myocardial regeneration strategies.