Adhesive interactions between cells regulate tissue integrity as well as the process of inflammatory cell recruitment. Such intercellular interactions are regulated by adhesion receptors and can be homotypic, that is, between cells of the same type, for example, between adjacent endothelial cells in the vasculature, as well as heterotypic, that is, between different cells, such as the leukocyte endothelial interactions that take place during leukocyte extravasation. Emerging evidence points to the importance of the family of junctional adhesion molecules (JAMs), which are localized in interendothelial contacts and are implicated in the regulation of leukocyte extravasation. JAMs are members of the immunoglobulin superfamily and can undergo both homophilic and heterophilic interactions. This chapter deals with the role of JAMs in the regulation of adhesive interactions between vascular cells.