The endothelial barrier function requires the adhesive activity of VE-cadherin and claudin-5, two key components of adherens and tight endothelial junctions, respectively. Emerging evidence that VE-cadherin controls claudin-5 expression by preventing the nuclear accumulation of FoxO1 and β-catenin, which repress the claudin-5 promoter, provides a crosstalk between these endothelial junctional structures.