Epithelial cells adhere to their neighbors and the extracellular matrix by means of adhesion complexes composed of transmembrane components connected to cytoplasmic proteins and the cytoskeleton. Recent results suggest that these complexes not only mediate adhesion but are also engaged in the transmission of signals from the plasma membrane to the nucleus to regulate gene expression. Main mediators of such signal-transduction processes are proteins that localize to sites of adhesion and the nucleus. Here, we review such signal-transduction pathways and discuss how they influence cell proliferation and differentiation.