A variety of InsP3-dependent Ca2+ signals coded in time, amplitude and space occur during the process of cardiac cell differentiation and heart development. Studies performed in both embryos and embryonic stem cell differentiating in cardiomyocytes have uncovered that Ca2+ regulates multiple steps of these biological processes in vertebrates. These include secretion of cardiogenic factors, cardiac transcriptional cascades and in turn gene expression, myofibrillogenesis and initiation of embryonic pacemaker activity. Evidence is accumulating to foresee Ca2+ as a major second messenger in directing the fate of stem cells and patterning the heart in the embryo.