Primary biliary cirrhosis is an uncommon chronic liver disease of unknown aetiology, affecting mostly women. It is characterised by progressive inflammation and destruction of the liver tissue, eventually progressing to liver cirrhosis and the need for liver transplantation. Methotrexate, a folic acid antagonist with immunosuppressive properties, has been used to treat patients with primary biliary cirrhosis. However, the evidence did not show a clear benefit of methotrexate on mortality or the need for liver transplantation in patients with primary biliary cirrhosis. This review is based on five randomised trials; four comparing methotrexate with placebo, and one comparing methotrexate with colchicine. Methotrexate, compared with placebo, has no significant beneficial effect on mortality and the need for liver transplantation is not significantly reduced. The effects of methotrexate on pruritus, fatigue, clinical complications, liver biochemistry levels, liver histology, and adverse events were not significantly different from placebo. There may be some beneficial effect on pruritus score (ie, an objective measure of subjective feeling of pruritus), but we cannot recommend methotrexate for this indication only, taken into account possible adverse events. In the small trial comparing methotrexate versus colchicine, methotrexate seemed to work superior to colchicine, but it is not clear if this stems from the fact that methotrexate exerts beneficial effects as colchicine exerts harmful effects. In comparison with both placebo and colchicine, methotrexate was associated with large risks of mortality and adverse events, but the increase did not reach statistical significance.