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Impairment of the protective properties of the blood-brain barrier (BBB) is a key event during numerous neurological diseases, including multiple sclerosis (MS). Under these pathological conditions, the specialized brain endothelial cells (BECs) lose their protective function leading to neuroinflammation and neurodegeneration. To date, underlying mechanisms for this loss of function remain unclear. Endothelial to mesenchymal transition (EndoMT) is a dynamic process by which endothelial cells (ECs) dedifferentiate into mesenchymal cells and as a result lose their specific phenotype and function. As yet, little is known about the involvement of this process in the impaired function of the BECs under pathological conditions such as MS. Interestingly, several signaling pathways that can induce EndoMT are also involved in different central nervous system (CNS) pathologies associated with BBB dysfunction. In this review, we first discuss the structure and function of the BBB highlighting the changes that occur during MS. Next, we will summarize recent findings on the pathways underlying EndoMT, and finally, we will discuss the potential role of EndoMT during BBB dysfunction in neurological disorders. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger., (Copyright © 2015 Elsevier B.V. All rights reserved.)