To continuously process neural activity underlying sensation, movement and cognition, the CNS requires a homeostatic microenvironment that is not only enriched in nutrients to meet its high metabolic demands but that is also devoid of toxins that might harm the sensitive neural tissues. This highly regulated microenvironment is made possible by two unique features of CNS vasculature absent in the peripheral organs. First, the blood–blood barrier, which partitions the circulating blood from the CNS, acts as a gatekeeper to facilitate the selective trafficking of substances between the blood and the parenchyma. Second, neurovascular coupling ensures that, following local neural activation, regional blood flow is increased to quickly supply more nutrients and remove metabolic waste. Here, we review how neural and vascular activity act on one another with regard to these two properties.