The cellular redox state has been increasingly recognized as a critical component of stress-induced cellular responses and disease. Inherent in these responses are reactive oxygen species (ROS), including • O 2 Ϫ , H 2 O 2 , and • OH, which inflict direct cellular damage in addition to acting as intracellular second messengers modulating signal transduction pathways. These intracellular highways of communication are critical in determining cell fates and whole-organ responses following environmental injury. Pathologic events caused by transient tissue hypoxia followed by oxygen reperfusion (ischemic/reperfusion [I/R]) are the cause of numerous types of surgical and environmentally induced injuries in the liver associated with transplantation and resection. Pathologic changes encountered following reperfusion of an ischemic organ include the immediate generation of ROS, as well as subsequent neutrophil-predominant inflammatory responses that lead to a second round of deleterious ROS generation at sites of damage. Recently, it has become increasingly appreciated that ROS are involved as second messengers in a number of cellular signaling events leading to the induction of AP-1 and nuclear factor-B pathways.