Development of blood vessels is coordinated by angiogenesis and stabilization of vascular endothelial cells (ECs). The vascular network is established during embryogenesis to supply oxygen and nutrients to the tissues and organs. However, after cardiac or peripheral ischemia is caused by occlusion of the vessels, new vessels must be formed to rescue the ischemic tissues. Many angiogenic growth factors and chemokines are produced in the ischemic tissue to induce angiogenic sprouting of preexisting vessels. Branched vessels must be again restabilized to form mature vessels that deliver blood to the tissues. To this end, vascular EC–cell adhesion is tightly regulated by cell–cell adhesion molecules and extracellular stimuli that activate G protein-coupled receptors and receptor tyrosine kinases exclusively expressed on vascular ECs. This review spotlights the recent studies of vascular endothelial cadherin and of sphingosine 1-phosphate signaling and angiopoietin-Tie signaling.(Circ J 2009; 73: 2183–2191)