The L-arginine/nitric oxide (NO) pathway has been recognized as a main regulator of several cell functions. Accordingly, there is an increasing number of pathophysiological conditions in which a precise knowledge of NO status could prove helpful in understanding the mechanisms involved in disease development, prevention and treatment. These include several hepatic disorders, such as liver cirrhosis and associated hyperdynamic circulation with portal hypertension, ischaemia-reperfusion injury occurring during liver transplantation, and chronic cholestatic conditions. Overall, NO seems to exert a dual role in the pathobiology of liver diseases: one mostly beneficial, due to its vasoactive effects; and one mostly negative, due to its local toxic effects. Protective actions are primarily mediated via vasodilation, antithrombosis, inhibition of neutrophil adhesion and inhibition of apoptosis. Deleterious effects are dependent upon the formation of highly reactive substances during oxidative stress. In this review aspects related to NO implications in the homeostasis of liver functions as well as in the pathogenesis of some relevant hepatic clinical syndromes will be discussed in view of possible therapeutic options.