Alcoholic liver disease involves significant crosstalk among intracellular signaling events in the liver. Overall, inflammatory and innate immune responses in Kupffer cells due to elevated gut-derived plasma endotoxin levels, increased reactive oxygen species-induced damage, and profibrogenic factors such as acetaldehyde or lipid peroxidation products contribute to activation of hepatic stellate cells, the key cell type involved in liver fibrosis. Using in vitro and in vivo approaches, there has been great progress in our understanding of the mechanisms leading to liver fibrosis: potential biomarkers of fibrosis have been identified, and several candidate targets for antifibrotic drugs have been elucidated.