The field NO research has contributed much to our understanding of cardiovascular disease since the discovery of endogenous NO in 1986.  The biological importance of NO was first shown by the findings that nitroglycerin causes vasodilation by liberating NO in the smooth muscle, and activating guanylate cyclase to raise smooth muscle levels of cyclic GMP. NO also inhibits platelet aggregation by cyclic GMP mechanisms.  The subsequent experiments on the mechanism by which NO activates guanylate cyclase and raises tissue cyclic GMP levels enabled investigators to better understand the possible causes of cardiovascular diseases.  The high pharmacological potency of NO was finally understood when NO was shown to be formed endogenously, and to be the same as EDRF. Based on these properties of NO, new drugs can be developed as vasodilators and antiplatelet agents for the treatment of a variety of vascular disorders including impotency. NO elicits many other actions in mammalian systems including inhibition of cell proliferation, airway bronchodilation, antimicrobial effects, other host defense effects, and also modulates learning and memory as well as other central functions. This allows for an extensive opportunity to develop novel drugs for the diagnosis, prevention and treatment of many different diseases, most of which are vascular in origin.  The complications of diabetes and impotency involve vascular disorders that may be treated by NO and related drugs.  Novel modes of therapy including gene transfer or gene regulation may soon be used to correct defects in the NO pathway, which can lead to new ways to treat many cardiovascular diseases.  In addition, new advances in reducing oxidative stress should lead to novel therapeutic measures of treating vascular disease.  These include modified statins, ACE inhibitors and AT1 receptor antagonists.  The antioxidant actions of these drugs and potential drugs are beneficial at least in part because they prevent the rapid destruction of NO and, thereby, enhance the biological actions of NO.