A tight regulation of the neuroparenchymal microenvironment is imperative for proper neurological function. The flux of blood-borne ions and solutes is restricted by specialized tissue barriers and of the three main central nervous system barriers, the brain endothelium constituting the blood-brain barrier represents the major interface between blood and brain. At the basis of the bloodbrain barrier are, next to an elaborate transporting machinery, tight junctions which create not only a paracellular diffusion constraint but also enable vectorial transport across the endothelial monolayer. Generally, tight junctions not only represent a cellcell adhesion structure, but integrate various signaling pathways via large multiprotein complexes, thereby impacting upon processes such as cell proliferation, cytoskeletal rearrangement, and transcriptional control. This review provides an overview of tight junction morphology and discusses our current understanding of the molecular composition of endothelial tight junctions at the blood-brain barrier.