Liver fibrosis is a highly dynamic process in which multiple genes interact with environmental factors. Recent human epidemiologic studies have identified possible polymorphisms in a number of candidate genes that influence the progression of liver fibrosis. These genetic factors could explain the broad spectrum of responses to the same etiologic agent found in patients with chronic liver diseases. Polymorphisms in genes encoding immunoregulatory proteins, proinflammatory cytokines, and fibrogenic factors may influence disease progression in patients with alcohol-induced liver disease, primary biliary cirrhosis, or chronic hepatitis C. However, some of the studies have yielded contradictory results. For example, conflicting results have been obtained in studies assessing the role of mutations in the hemochromatosis gene on fibrosis progression in patients with chronic hepatitis C. Large-scale, well-designed studies are required to clarify the actual role of this factor and other genetic variants in liver fibrosis.