Leptin is a 16-kDa nonglycosylated protein primarily secreted from the adipocytes of white fat; minor levels of regulated leptin expression also occurs at other sites such as placenta, skeletal muscle, the stomach fundus, and culture-activated hepatic stellate cells (HSCs). Leptin is primarily involved in the regulation of food intake and body composition through a central feedback mechanism linking food ingestion, hypothalamus, and adipose tissue mass. In recent years, however, emerging evidence has suggested a critical role of leptin in hepatic inflammation and fibrogenesis and the influence of leptin on chronic liver disease has been an area of active research worldwide. In this review the data on the in vivo and in vitro actions of leptin on liver cells in experimental animal models of liver injury and the effects of leptin on human liver are discussed, with a focus on three distinct fields of chronic liver diseases: nonalcoholic steatohepatitis, alcoholic liver disease, chronic viral hepatitis, and, especially, hepatitis C.