Abstract Primary biliary cirrhosis (PBC) is a chronic, progressive, cholestatic disease of unknown aetiology that affects mainly women. There is a strong association with antimitochondrial antibodies (AMA) and the disease is characterized by granulomatous cholangitis, which leads to progressive destruction of the small and middle-sized intrahepatic bile ducts, leading to fibrosis and cirrhosis. Patients with PBC may present with itching or tiredness: both symptoms are commonly seen in practice, but PBC is seldom the cause. However, because of the benefit of making a diagnosis, the opportunity for treatment and diagnosis of complications of liver disease and other autoimmune conditions associated with PBC (such as thyroid disease, sicca syndrome, Raynaud’s and coeliac disease), the condition must be considered, If in doubt, blood tests for liver function and the presence of AMA should clarify the diagnosis. Treatment is largely symptomatic with the use of colestyramine as the main treatment for pruritus, although agents as rifampicin, naltrexone or even plasmapheresis is effective in some. Lethargy is difficult to treat but may respond to Modafenil. Bile acids (ursodeoxycholic acid) 10–15 mg/kg/day may slow progression. Transplantation is the only effective treatment for end-stage disease but the condition recurs in about 50% at 10 years. The pathogenesis is not clear but laboratory, GWAS and clinical associations suggest an autoimmune disease but postulated triggers include bacterial, mycobacteria, retrovirus and other environmental factors.