Cell to cell junctions direct endothelial responses both in quiescent and angiogenic vessels. Endothelial cells express both tight and adherens junctions. Although different in their specific molecular composition, these junctional complexes present a relatively similar structural and functional arrangement. Transmembrane adhesive proteins that bind homophilically identical molecules on adjacent cells represent the core component in both types of junctions. This intercellular recognition starts a sequence of signaling events. Signal transmission is mediated through the interaction with cytoplasmic and transmembrane partners. Adherens junctions are ubiquitous along the vascular tree. In these structures VE-cadherin and its intracellular partners mediate adhesion. In vitro and in vivo data show that VE-cadherin is required for endothelial integrity in quiescent vessels and for the correct organization of new vessels. VE-cadherin regulates endothelial functions through different mechanisms which include: (i) direct activation of signaling molecules such as PI3kinase and Rac, to sustain survival and organization of the actin cytoskeleton; (ii) regulation of gene transcription, possibly modulating the nuclear level of transcription co-factors such as beta-catenin and p120; (iii) formation of complexes with growth factor receptors, such as the type 2 receptor of VEGF (VEGFR-2) and modulation of their signaling properties.