Lining the inner surface of the circulatory system, the vascular endothelium accomplishes a vast variety of specialized functions. Even slight alterations of these functions are implicated in the development of certain cardiovascular diseases that represent major causes of morbidity and mortality in developed countries. Endothelial mitochondria are essential to the functional integrity of the endothelial cell as they integrate a wide range of cellular processes including Ca²⁺ handling, redox signaling and apoptosis, all of which are closely interrelated. Growing evidence supports the notion that impairment of mitochondrial signaling in the endothelium is an early event and a causative factor in the development of diseases such as atherosclerosis or diabetic complications. In this review, we want to outline the significance of mitochondria in both physiology and pathology of the vascular endothelium.