Nitric oxide(NO) is an important messenger and effector involved in the regulation of many physiological functions in the mammalian body. Dysfunction of NO formation has been implicated in the pathogenesis of a number of disorders. In this article, general aspects on biosynthesis and pathophysiology of NO were briefly reviewed, but major focus was placed on recent advances in the research of NO modulators including NO donors and NO synthase inhibitors. Finally, an outlook on the future development of NO modulators was provided.