This review concentrates on the influence of folate supplementation on the toxicity and efficacy of methotrexate (MTX) in rheumatoid arthritis patients. The design, type of folate supplementation and timing of supplementation vary considerably between the six published controlled studies. Folate supplementation seems to have no effect on the efficacy of MTX but may influence toxicity in a favourable way. Further studies are needed to assess the type of supplementation (folic acid, folinic acid), the predisposing factors for toxicity and cost effectiveness.