Cerebral endothelial cells accomplish numerous tasks connected to the maintenance of homeostasis of the central nervous system. They create a barrier between the central nervous system and peripheral blood and regulate mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. In pathophysiological conditions (e.g., stroke or ischemia-reperfusion injury) the endothelial functions are impaired, leading to increased vascular permeability, vascular inflammation, leukocyte-endothelium interactions, and transendothelial migration, driving CNS inflammation and neuronal destruction. This review describes the current knowledge on the regulatory roles of endothelial cells in neuroinflammatory processes.