The vascular endothelium is the innermost layer of blood vessels and is a key regulator of vascular tone. Endothelial function is controlled by receptor signaling through G protein-coupled receptors, receptor tyrosine kinases and receptor serine-threonine kinases. The β-arrestins, multifunctional adapter proteins, have the potential to regulate all of these receptor families, although it is unclear as to whether they serve to integrate signaling across all of these different axes. Notably, the β-arrestins have been shown to regulate signaling by a number of receptors important in endothelial function, such as chemokine receptors and receptors for vasoactive substances such as angiotensin II, endothelin-1 and prostaglandins. β-arrestin-mediated signaling pathways have been shown to play central roles in pathways that control vasodilation, cell proliferation, migration, and immune function. At this time, the physiological impact of this signaling has not been studied in detail, but a deeper understanding of it could lead to the development of novel therapies for the treatment of vascular disease.