One of the most interesting questions in vascular biology is how cells circulating under high shear flow in the bloodstream can selectively target a particular site on the blood vessel wall and fulfil their specialized functions. In the inflammatory response, neutrophils, monocytes or lymphocytes roll on activated endothelial cells before sticking, and then transmigrating through the endothelium to reach the site of damaged tissue. In haemostasis, platelets adhere to the subendothelial matrix of a damaged vessel wall, spread over the surface and recruit more platelets to form a platelet aggregate or thrombus. Cell adhesion is also critical in the pathological processes of atherogenesis and thrombosis. Each stage of vascular cell adhesion is regulated by specific receptors on the cell surface that control cell-cell and cell-matrix interactions. Many of these adhesive receptors not only regulate contact adhesion, but also initiate signals that activate the cell and regulate post-adhesion cellular events. These include the cytoskeletal rearrangements involved in cell shape change and motility, secretion from storage organelles, and expression of additional activation-dependent receptors. PECAM-1 (platelet-endothelial cell adhesion molecule-1; CD31) is an adhesive receptor found on endothelial cells, platelets and leukocytes that plays a key role in regulating leukocyte migration through endothelial cell junctions. Recent evidence also suggests that PECAM-1 regulates the adhesive function of integrin receptors on leukocytes, and that cytoplasmic phosphorylation of PECAM-1 in platelets is associated with activation-dependent rearrangement of cytoskeletal actin filaments. This review will examine the structure of PECAM-1 and its role in vascular biology. Interestingly, many characteristics of PECAM-1 structure, function and regulation are shared by other adhesive receptors found on vascular cells.