Endothelial dysfunction is known to be early stage of atherosclerosis and its presence leads to poor prognosis. Recently many basic researchs were done to elucidate the basic mechanism related to endothelial nitric oxide synthase (eNOS). eNOS is composed of dimer, between which calmodulin binding domain is located. This area plays important role in producing NO with BH4 (tetrahydrobiopteryn as a co factor). In the presence of excess of superoxide from NADPH oxidase, NO binds with superoxide to be peroxynitrite. BH4 is converted to BH2 in the presence of peroxynitrite and eNOSdimer dissociates to monomer, which is called uncoupling. Uncoupled eNOS produces superoxide and it results in endothelial dysfunction. NO deficiency is related to the decreased number of peripheral endothelial progenitor cell and HDL-cholesterol is known to stimulate eNOS. This would be new field of research relating eNOS to atherogenesis and eNOS's role in prevention of cardiovascular disease.