Liver ®brosis can be considered as a dynamic and highly integrated cellular response to chronic liver injury [1]. Whatever the etiology, the evolution of chronic liver disease (CLD) is characterized by perpetuation of parenchymal necrosis, chronic hepatitis and qualitative as well as quantitative alterations in extracellular matrix (ECM) composition, whereas activation of hepatic stellate cells (HSC) and involvement of macrophages and Kupffer cells predominate at cellular level [1±3]. At the molecular level, growth factors, cytokines and chemokines, changes in ECM organization and composition as well as reactive molecules originated by oxidative stress have been suggested to play a pathogenetic role [1±3]. Evidence of oxidative stress has been detected in almost all the clinical and experimental conditions of CLD with different etiology and ®brosis progression rate (Table 1 and Refs. [4±6]), often in association with decreased antioxidant defenses. As already proposed for atherosclerosis [7] and chronic degenerative diseases of CNS [8], oxidative stress-related molecules may act as mediators able to modulate tissue and cellular events responsible for the progression of liver ®brosis [1,3± 6]. This review will highlight major concepts and recent insights in the ®eld, and the de®nition `oxidative stressrelated molecules’ will be used to indicate reactive oxygen intermediates (ROI, i.e. oxygen-centered free radicals or intermediates) as well as aldehydes from lipid peroxidation (i.e. a major feature of hepatic oxidative stress). Major concepts and ®ndings related to the role of nitric oxide (NO) and reactive nitrogen oxide intermediates (RNOI) in chronic liver injury, with special reference to NO interactions with ROI and potential anti®brogenic action of NO, will be also presented. 2. Oxidative stress in CLD: basic and clinically relevant concepts