In metazoans, the Notch pathway is one of the crucial pathways that regulate cell fates and tissue formation during development. Moreover, Notch has also been implicated in the regenerative capacity of adult self-renewing tissues. Notch signaling mediates local cell-cell communication via interaction of the Notch receptors with a membrane-bound ligand of the Delta-Serrate-LAG-2 family. Accumulating evidence suggests that aberrant Notch signaling is implicated in a variety of human diseases. In the heart, Notch controls several key processes during cardiac morphogenesis. In particular, Notch plays an important role in the commitment between the mesodermal and neuroectodermal lineages and seems to regulate cardiogenesis in mesodermal precursors.