The blood–brain barrier is part of the neurovascular unit and serves as a functional and anatomical barrier between the blood and the extracellular space. It controls the flow of solutes in and out of the brain thereby providing an optimal environment for neuronal functioning. Paracellular transport between endothelial cells is restricted by tight junctions and transendothelial transport is reduced and more selective compared to capillaries of other organs. Further, the blood–brain barrier is involved in controlling blood flow and it is the site for signaling damage of the nervous system to the peripheral immune system. As an important player in brain homeostasis, blood–brain barrier dysfunction has been implicated in the pathophysiology of many brain diseases including stroke, traumatic brain injury, brain tumors, epilepsy and neurodegenerative disorders. In this article – highlighting recent advances in basic science – we review the features of the blood–brain barrier and their significance for neuronal homeostasis to discuss clinical implications for neurological complications following cerebral ischemia.