Kupffer cells (KC) constitute 80–90% of tissue ­macrophages present in the body. These liver macrophages are named after the pathologist C. von Kupffer, who apparently first recognized this nonparenchymal cell type 1. KC represents about 35% of the nonparenchymal liver cells in normal adult mice 2. They reside within the lumen of the liver sinusoids, adherent to the endothelial cells that compose the blood vessel walls. KC, found in greatest number in the periportal area, constitute the first macrophage population of the body to come in contact with bacteria, bacterial endotoxins, and microbial debris derived from the gastrointestinal tract and transported to the liver via the portal vein 3. Consequently, KC are constantly exposed to proinflammatory factors, e.g., bacterial endotoxins, known to activate macrophages. Upon activation, KC release various products including cytokines, prostanoides, nitric oxide, and reactive oxygen species 4. These factors regulate the phenotype of the KC that produce them, as well as the phenotypes of neighboring cells, such as hepatocytes, stellate cells, and endothelial cells and other immune cells that traffic through the liver 5. Therefore, KC are intimately involved in the liver’s response to infection, toxins, ischemia, resection, and various other stresses. This review will summarize established basic concepts of KC function as well as their role in the pathogenesis of various liver diseases. Due to the complexity of processes mediated by KC, this review focuses on selected aspects of the pathophysiology.