Cellular interactions with the extracellular matrix and with neighboring cells profoundly influence a variety of signaling events including those involved in mitogenesis, survival, and differentiation. Recent advances have provided insights into mechanisms underlying the ability of integrins, cadherins, selectins, and other cell adhesion molecules to regulate signal transduction cascades. These mechanisms often involve the ability of cell adhesion molecules to initiate the formation of organized structures or scaffolds that permit the efficient flow of information in signaling pathways.