Methotrexate and leflunomide are both effective drugs in the treatment of patients with rheumatoid arthritis. Methotrexate has been available for many years, whereas leflunomide is a relatively new drug. Several large trials describing its efficacy and safety in comparison with both sulfasalazine and methotrexate and with placebo have been published recently. It appears that leflunomide is approximately equally effective as sulfasalazine and methotrexate. New data are also available on the mechanism of action of leflunomide especially. This drug probably acts as an immunomodulatory agent by interfering with the de novo synthesis of pyrimidines.