Primary biliary cirrhosis (PBC) is a chronic progressive disease of the intrahepatic bile ducts that primarily affects middle-aged women. The characteristic features include pruritus and lethargy. Although there is a widespread disturbance of the immune system, with association with other autoimmune diseases such as thyroid disease, sicca syndrome and Raynaud’s syndrome, elevation of immunoglobulins (especially IgM) and auto-antibodies; antibodies to the mitochondrial antigen PDC-E2 and to the nuclear-pore complex gp210, are almost diagnostic of the condition. The characteristic histology is of a granulomatous cholangitis. Diagnosis is made on the symptoms, laboratory tests showing cholestatic features (elevation of serum alkaline phosphatase and, later in the disease, in the serum bilirubin), characteristic immunology (raised IgM and anti-mitochondrial antibodies) and exclusion of other causes of cholestasis; liver biopsy may be indicated where there is doubt. Progression to end-stage liver disease occurs in about 25%. There is no effective treatment to halt progression although the bile acid, ursodeoxycholic acid, may slow progression. Liver transplantation is indicated for selected patients with end-stage disease; although recurrence may occur in the graft, this is of little significance and results are excellent. Treatment of the itching (which may be associated with increased opioid tone) is most effective with cholestyramine, although some benefit has been shown with rifampicin, naltrexone, sertraline and with plasmapheresis and some forms of extracorporeal dialysis (such as MARS); there is no effective treatment for the lethargy. Patients should be monitored for complications of cholestasis, cholestasis and cirrhosis. Overlap syndromes with autoimmune hepatitis may occur.