These proceedings review and discuss the different aspects of the biology of the Blood-Brain Barrier (BBB) and its involvement in the pathogenesis of brain disorders. The BBB, formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages and a basal membrane, serves as a controlled functional gate to CNS. In vitro and in vivo models have been established to study the cellular and molecular interaction within the BBB and between the BBB and the neural cells. The structural and functional integrity of the BBB was shown to be dramatically altered during various diseases of the CNS, including neoplasia, ischemia, trauma, inflammation and bacterial and viral infections. Two approaches to drug delivery across the BBB have been pursued, based on either modulation of the permeability of the barrier or by conjugation of the drug to substrates of the active transport systems of the BBB.