The blood–brain barrier (BBB) constitutes an elaborate structure formed by specialized capillary endothelial cells, which together with pericytes and perivascular glial cells regulates the exchanges between the central nervous system (CNS) and the periphery. Intricate interactions between the different cellular constituents of the BBB are crucial in establishing a functional BBB and maintaining the delicate homeostasis of the CNS microenvironment. In this review, we discuss the role of astrocytes and microglia in inducing and maintaining barrier properties under physiological conditions as well as their involvement during neuroinflammatory pathologies. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.