The integrity of all organ systems requires faithful interaction between its component cells and the extracellular matrix (ECM). In the central nervous system (CNS), matrix adhesion receptors are uniquely expressed by the cells comprising the microvascular compartment, and by neurons and their supporting glial cells. Cells within the cerebral microvasculature express both the integrin and dystroglycan families of matrix adhesion receptors. However, the functional significance of these receptors is only now being explored. Capillaries of the cerebral microvasculature consist of the luminal endothelium, which is separated from circumferential astrocyte end-feet by the intervening ECM of the basal lamina. Endothelial cells and astrocytes cooperate to generate and maintain the basal lamina and the unique barrier functions of the endothelium. Integrins and the dystroglycan complex are found on the matrix-proximate faces of both endothelial cells and astrocyte end-feet. Pericytes rest against the basal lamina. In the extravascular compartment, select integrins are expressed on neurons, microglial cells, and oligodendroglia. Significant alterations in both cellular adhesion receptors and their ligands occur under the conditions of focal cerebral ischemia, multiple sclerosis (MS) and the modeled condition experimental autoimmune encephalomyelitis (EAE), certain tumors of the CNS, and arteriovenous malformations (AVMs). The changes in matrix adhesion receptor expression in these conditions support their functional significance in the normal state. We propose that matrix adhesion receptors are essential for the maintenance of the integrity of the blood–brain permeability barrier, and that modulation of these receptors contribute to alterations in the barrier during brain injury. This review examines current information about cell adhesion receptor expression within the cerebral microvasculature and surrounding tissue, and their potential roles during the vascular responses to local injury.