Leflunomide (Arava), Aventis Pharmaceuticals) is an immunomodulating drug that interferes with the metabolism of pyrimidine by inhibiting dihydro-orotate dehydrogenase (DHO-DH) in mitochondria, thereby blocking T- and B cell proliferation. Antibody production is also affected by DHO-DH blockade. Other immunomodulatory effects of leflunomide have also been reported. Symptomatic and structural effects of leflunomide in active rheumatoid arthritis have been strictly evaluated by double-blind, randomised, placebo-controlled studies that were aimed at validating its use in rheumatoid arthritis. Further trials are now required to confirm efficacy and safety of this drug in combination with other agents.