The Drosophila melanogaster gene Notch is central to many cell differentiation events during development. It encodes a large transmembrane signal receptor protein that acts in a poorly understood mechanism of communication affecting the choice of alternative differentiation fates by cells in close proximity. Genes with homology to Notch have been isolated from the nematode Caenorhabditis elegans and a number laboratories, including our own, have isolated multiple vertebrate Notch homologs. In this article we briefly outline the current state of research on Notch and our contribution to it. First, we examine the structure of Notch-related proteins. We then examine the requirements for Notch activity in the development of different organisms and how genetic and transgenic studies are helping us to understand the mechanism(s) by which these proteins function. We present models for the action of Notch receptors during signal transduction and for the interaction of multiple vertebrate Notch receptors. Finally, we discuss current ideas about the role played by Notch in differentiation and cell-cell communication.