There are 12 non-controlled and only two controlled studies using methotrexate (MTX) in a total of 207 SLE patients in the literature. The majority of these studies evaluated mainly cutaneous and/or articular involvement and attained good results. Two studies evaluated a small number of patients with lupus nephritis, achieving discordant results. Two other studies in pediatric onset systemic lupus erythematosus (SLE) also presented conflicting results, it being relevant that the one with poor response had the majority of patients with nephritis. One of the controlled trials was retrospective and concluded that MTX was effective in the treatment of antimalarial-resistant lupus arthritis and that toxicity leading to discontinuation of MTX was infrequent. The other controlled study was a double-blind, randomized, placebo-controlled clinical trial that evaluated SLE patients with mild activity. The authors concluded that MTX was effective in controlling cutaneous and articular activity and permitted prednisone dose reduction. The side effects were frequent but only 10% of patients needed to discontinue the medication. The accumulative evidence suggests that MTX in a low weekly dose may be effective in SLE patients with articular and/or cutaneous involvement with no response to antimalarials and low-dose prednisone and in patients in whom we can not reduce prednisone dose due to articular or cutaneous activity. Caution is required concerning the side effects.