Leukocytes, i.e., neutrophils, monocytes, and lymphocytes, can accumulate in the hepatic vasculature and contribute to the pathophysiology of various liver diseases. Recently, significant progress has been made in the understanding of the basic mechanisms of neutrophil infiltration and cytotoxicity in the liver. However, there are a substantial number of unresolved issues. This article describes the current knowledge and the gaps in our understanding of mechanisms of neutrophil sequestration in sinusoids and venules, adhesion to endothelial cells, and transmigration and adherence to parenchymal cells. From these data, it is clear that assumptions regarding the roles of adhesion molecules in the liver may be misleading if drawn from studies of peripheral vascular beds. Greater insight into these mechanisms is critical for the development of selective therapeutic strategies that attenuate excessive inflammatory responses without compromising the vital host defense.