Embryonic Stem (ES) cells have the potential to differentiate into many cell types, including spontaneously beating cardiomyocytes. It has been hoped that they might serve as a source for donor tissue to treat a number of diseases including heart damage, however, even under ideal culture conditions, only a small percentage of ES cells differentiate into cardiomyocytes. This is due, in part, to an incomplete understanding of the earliest steps of cardiac determination. Work in a number of animal systems including mouse and amphibians suggest that the decision to become cardiac is made during the earliest stages of mesoderm formation and so, in order to study this process effectively I use animal models in which very young embryos are readily accessible and easy to manipulate. Xenopus laevis, the African claw-toed frog is an ideal system for such studies and I have used both Xenopus embryos and mouse Embryonic Stem Cells to study the mechanisms involved in establishing the heart field and have translated those studies to the problem of achieving efficient differentiation of cardiomyocytes from mouse ES cell culture.