Primary biliary cirrhosis (PBC) is considered a model autoimmune disease because of the similarities between patients, their relative homogeneous presentation and natural history, and the presence of the signature autoantibody, the antimitochondrial antibodies. PBC also illustrates the potential role of genetic and environmental influence and is unique in having several well-defined animal models that recapitulate distinct features of the disease. The pathogenesis of the disease includes genetic predisposition, the production of both innate and adaptive immune responses, and cholangiocyte-specific biology that addresses the specificity of disease. In this review we highlight these features of PBC in comparison to other autoimmune diseases.