Connexins are single polypeptides that assemble to form paired connexon hexamers participating in gap-junctional intercellular communication. In addition, unpaired connexons at cell membrane also act as channels connecting cytosols and extracellular space. These channels' properties plus other unique functions of connexins give the molecules significant roles in endothelial cells, which mainly express connexin43 (Cx43), Cx40, and Cx37. In vitro studies have shown that expression of endothelial connexins are regulated by both physiological and pathological factors, a majority of which are involved in atherogenesis. In vascular disorders, endothelial connexins are differentially regulated. However, down-regulation of gap junctions is a common phenomenon. These findings suggest that reduced expression of endothelial gap junctions is a potential indicator of endothelial dysfunction and warrant investigators to explore the molecular mechanisms as well as therapeutic implications.