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The endothelium plays important roles in modulating vascular tone by synthesizing and releasing a variety of endothelium-derived relaxing factors, including vasodilator prostaglandins, NO, and endothelium-dependent hyperpolarization factors, as well as endothelium-derived contracting factors. Endothelial dysfunction is mainly caused by reduced production or action of these relaxing mediators. Accumulating evidence has demonstrated that endothelial functions are essential to ensure proper maintenance of vascular homeostasis and that endothelial dysfunction is the hallmark of a wide range of cardiovascular diseases associated with pathological conditions toward vasoconstriction, thrombosis, and inflammatory state. In the clinical settings, evaluation of endothelial functions has gained increasing attention in view of its emerging relevance for cardiovascular disease. Recent experimental and clinical studies in the vascular biology field have demonstrated a close relationship between endothelial functions and cardiovascular disease and the highlighted emerging modulators of endothelial functions, new insight into cardiovascular disease associated with endothelial dysfunction, and potential therapeutic and diagnostic targets with major clinical implications. We herein will summarize the current knowledge on endothelial functions from bench to bedside with particular focus on recent publications in Arteriosclerosis, Thrombosis, and Vascular Biology.