Intercellular adhesion plays a key role during development and maintenance of tissue homeostasis. Within the vascular system, cell-cell adhesion is particularly important for the correct formation, networking, and remodeling of vessels. Although in vascular endothelial cells adhesive junctions account for the integrity of the vessel wall, they are not to be considered as static molecular structures that function as intercellular glue. This becomes evident during the remodeling of the endothelium in various physiological and pathological processes, requiring highly dynamic vascular adhesion complexes. Moreover, it has recently become evident that, besides their structural functions, adhesion molecules involved in endothelial cell-cell interaction play an important role in inducing and integrating intracellular signals that, in turn, impact on several aspects of vascular cell physiology. In this review, we describe these recent findings focusing on junctional proteins at adherens and tight junctions. The role of this adhesion molecule-mediated signaling is discussed in the context of developmental and pathological angiogenesis.