Cell adhesion is critical for the genesis and maintenance of both three-dimensional structure and normal function in tissues. The biochemical entities mediating cell adhesion are multiprotein complexes comprising three broad classes of macromolecules: the adhesion receptors, the extracellular matrix molecules, and the adhesion plaque proteins (Gumbiner, 1996). Cell adhesion receptors are typically transmembrane glycoproteins that mediate binding to extracellular matrix (ECM) b molecules or to counter-receptors on other cells; these molecules determine the specificity of cell-cell or cell-ECM interaction. The ECM proteins are usually fibrillar in nature and provide a complex structural and functional network that can interact simultaneously with multiple cell surface receptors. The intracellular plaque proteins (or peripheral membrane proteins) provide structural and functional linkages between adhesion receptors and the actin microfilaments, microtubules, and intermediate filaments of the cytoskeleton. An exciting concept that has emerged from recent cell biological research is that cell adhesion complexes are not simply static architectural entities. Rather, they are dynamic units that are capable of capturing and integrating signals from the extracellular environment (Rosales et al., 1995). Moreover, the functions of cell adhesion complexes are regulated precisely by biochemical events within the cell. Thus cell adhesion receptors are at a nexus of two-way signaling between the cell and its external environment. This review will examine current knowledge concerning signal transduction events initiated or modulated by cell adhesion receptors. The emphasis will be on the integrin family of receptors because their signaling functions have been studied more extensively than those of other adhesion receptor families. However, we also will examine signaling events involving the cadherin, immunoglobulin-cell adhesion molecule (Ig-CAM), and selectin families of adhesion receptors. Adhesion-mediated signaling influences several critical cellular processes including gene expression, cell cycle, and programmed cell death; these aspects will be explored. However, the major emphasis of this review will be on mechanisms of adhesion receptor signaling.