Primary biliary cirrhosis (PBC) is characterized by unknown etiologies, anti-mitochondrial antibodies, injury of the biliary duct and the lack of a definite remedy. The etiologies of PBC have been well-discussed, including microorganisms and xenobiotics as the triggers for initiating the disease, and an abnormality of immune-tolerance. Recently, several animal models of PBC have been developed that may lead to the development of new therapies. Here, we reviewed the articles that address the etiology of PBC and the therapy for this disease for the confirmation of our current positions and future directions.