Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, most commonly affecting female patients between 40 and 60 years of age. Patient sera present autoantibodies against mitochondrial antigens (AMA) and elevated serum IgM. Histologic studies demonstrate progressive destruction of small- and medium-sized intrahepatic bile ducts and, ultimately, liver cirrhosis. The precise mechanisms leading to selective destruction of such biliary epithelial cells are still unknown, although a number of immunomediated pathways have been proposed. Genetic background is critical in determining susceptibility to the disease, although no clear association with haplotypes of the major histocompatibility complex has been identified. Molecular mimicry by either infectious agents or xenobiotics has been proposed as a means of breaking tolerance in genetically predisposed individuals, thus leading to the onset of PBC. In this review, available data and current theories regarding the immunomediated pathogenesis of PBC will be described.