Primary biliary cirrhosis is an autoimmune disease of unknown etiology leading to progressive destruction of small intrahepatic bile ducts and eventually to liver cirrhosis and failure. It is characterized by female predominance (with most cases observed between the ages of 40 and 60) and serum autoantibodies to mitochondrial antigens as highly specific hallmarks. Epidemiologic data indicate a variable incidence and prevalence of the disease. A number of genetic factors have been indicated as playing a role in determining disease susceptibility or progression, although no definitive conclusion has been reached so far. However, as suggested by some epidemiologic observations, a number of environmental factors, including molecular mimicry by either microorganisms or xenobiotics, have also been proposed. A hypothesis gaining support is that environmental factors may trigger disease in genetically predisposed individuals. In this review, the available data regarding the epidemiology and pathogenesis of primary biliary cirrhosis will be described and discussed.