© 2004 Elsevier Ltd. All rights reserved. This chapter addresses the critical role of reactive oxygen and nitrogen species in alcohol-induced liver injury with specific emphasis on the mechanisms by which alcohol stimulates the production of these reactive species in mitochondria and the way their production negatively impacts mitochondrial function and disrupts hepatic energy conservation. It is widely believed that one component contributing to alcohol-induced liver pathology is the diminished capacity of the liver to generate Adenosine Triphosphate (ATP) and to maintain adequate ATP levels following exposure to alcohol chronically. This resulting decrease in hepatic energy ultimately leads to losses in hepatocyte viability, which has been identified as a critical factor contributing to the development of pathology. There are two mechanisms to generate ATP within the hepatocyte: glycolysis and the mitochondrial oxidative phosphorylation system. It is known that chronic alcohol consumption negatively impacts both of these cellular processes. This chapter focuses on the way chronic alcohol consumption disrupts mitochondrial mechanisms involved in ATP synthesis. Moreover, chronic alcohol-related alterations in mitochondria structure and function stimulate production of reactive oxygen species in liver mitochondria. This increase in oxidants could result in oxidative modification and possibly inactivation of mitochondrial macromolecules, thereby further contributing to mitochondrial dysfunction.