C hronic liver disease is almost always characterized by increased oxidative stress, regardless of the cause of liver disease. 1 Oxidative stress, defined as an imbalance between the oxidant and antioxidant systems, occurs due to a number of mechanisms. Activation of molecular oxygen as reactive oxygen species (ROS) is part of aerobic life that regulates diverse cellular functions, including signal transduction pathways, gene expression, growth, and death. ROS can help the organism in many ways-for example, by destroying invading pathogens. However, excessive ROS are toxic to the cell, because they can react with lipids, proteins, and DNA to alter their functions. [1][2][3] In hepatocytes, mitochondria and cytochrome P450 enzymes are the main sources of ROS. In addition, activated Kupffer cells and infiltrating inflammatory cells, in particular neutrophils, are also sources of ROS for the injured and inflammed liver. During inflammation, there is often increased production of nitric oxide. ROS can react with nitric oxide to generate peroxinitrite, a strong oxidizing agent that can interfere with SH-containing enzymes and help propagate lipid peroxidation. Many other reactive nitrogen species can also promote nitrosylation to alter protein structure and function beyond that caused by ROS alone. Nitrosative stress occurs when the ability to neutralize and eliminate reactive nitrogen species is overwhelmed. Major antioxidants within the cell include glutathione (GSH), tocopherol (vitamin E), and vitamin C. Key enzymes that participate in the removal of ROS are superoxide dismutase, GSH peroxidase, and catalase. In acute and chronic liver injury, there is often increased production of ROS coupled with reduced capacity to defend against ROS. [1][2][3]