Endothelial cells form a monolayer lining all blood and lymph vessels and the heart cavity. The strategic location of these cells at the interface between the flow of blood and surrounding tissues makes this "organ" multifunctional. Indeed, endothelial cells form a semipermeable barrier involved in local control of vascular tone, regulation of blood coagulation and adhesion of inflammatory cells, control the permeability of blood vessels or the process of angiogenesis. Many, if not all of these regulatory mechanisms involve a calcium signal. Ca2+ is an intracellular second messenger involved in a wide range of physiological processes. But the process of Ca2+ entry in nonexcitable cells such as endothelial cells remains an enigma that is the subject of intense investigations. In these cells, in contrast to excitable cells, the channels involved in Ca2+ entry are not activated by membrane depolarization. The calcium signal consists of two phases: the addition of an agonist is followed by release of Ca2+ from the endoplasmic reticulum (ER) after the opening of the inositol 1,4,5-triphosphate (IP3). This initial elevation of cytosolic Ca2+ is accompanied by a Ca2+ entry from the extracellular medium, thereby prolonging the Ca2+ signal.