Primary biliary cirrhosis (PBC) is a chronic cholestatic disease affecting middle-aged women. In addition to the potential for liver-related morbidity and mortality, it is recognized that patients with PBC frequently suffer from a marked impairment in their quality of life. In various studies fatigue has been identified as one of the principal factors contributing to this functional impairment in patients with PBC. It is also considered as a negative prognostic factor. In this article we discuss the pathogenesis and clinical issues related to chronic fatigue in PBC.