Studies have shown gender dimorphic response of the liver for various hepatic stresses including ischemia/reperfusion, hemorrhagic shock-resuscitation, hepatectomy, liver cirrhosis, endotoxemia, and chronic alcoholic consumption. The mechanisms responsible for the gender dimorphic response include differences in pro-inflammatory cytokine release, production of reactive oxygen species, and alteration in hepatic vasoregulatory action. These effects were shown to be modulated by circulating sex steroid levels. In this regard, modulation of sex steroid levels by agents/drugs has been proposed as a therapeutic option for preventing hepatic damage in various hepatic stress models. Further elucidation of precise mechanisms responsible for the gender-related differences in the hepatic pathophysiology is essential for the potential clinical application of sex hormone modulation therapy. In this article, current progress in our understanding the gender difference in the hepatic pathophysiology under the condition of hepatic stress is reviewed and discussed. © 2005 Elsevier Inc. All rights reserved.