The Notch pathway is now firmly established as a key signaling system for embryonic cardiovascular development as well as some adult pathologies in vertebrates. We have identified Hey bHLH transcriptional repressors as critical, but partly redundant transducers of these signals. Hey proteins control cardiomyocyte differentiation, epithelial to mesenchymal transition of endocardial cells, and a number of key features of arterial endothelial cells with corresponding defects in knockout mice. While most of the phenotypes are described in embryonic development, there is increasing evidence for additional adult pathologies. Despite the functional importance of Hey proteins little is still known about their molecular targets and interactions.