The vascular endothelium plays many important functions and its mechanical failure or abnormal operation may have serious consequences to health and even life of the organism. It controls the contraction and relaxation of blood vessels, affects the inflammatory processes, immune response and blood clotting and regulation of the permeability and integrity of the vessel wall. Impaired secretion of nitric oxide and prostacyclin 2, whose secretion is calcium concentration dependent, indicates endothelial dysfunction. Calcium is very important in many processes typical for vascular endothelium and is essential for proper functioning. Oxidative stress, induction of pro-inflammatory response and, consequently, a significant increase in the production of reactive oxygen species are a cause of damage in the vascular endothelium. In this paper we will discuss selected issues concerning the functioning of the vascular endothelium in normal and pathological conditions, as well as their connection point at the regulation of calcium signaling in these cells.