Neutrophils are involved in organ damage induced by an excessive acute inflammatory response after ischemia-reperfusion, trauma, and sepsis. In addition to causing vascular injury, neutrophils can transmigrate and attack parenchymal cells. This review summarizes recent advances in our understanding of neutrophil-induced parenchymal cell injury using the liver as an example. Reviewed are the mechanisms of neutrophil sequestration in the hepatic vasculature, transendothelial migration, adherence to hepatic parenchymal cells, and mechanisms of cytotoxicity. Discussed are the involvement of various adhesion molecules in these processes, the role of cytokines and chemokines in the pathophysiology, as well as the effects of proteases and reactive oxygen species released by neutrophils. The emerging understanding of the basic mechanisms of neutrophil-induced organ damage is critical for the development of therapeutic strategies to attenuate excessive acute inflammatory responses without compromising essential host defense mechanisms.