Methotrexate(MTX) is an antifolic agent and has been widely used for RA since early 1980s. Since 1999 when MTX was approved as an antirheumatic drug in Japan, patients taking MTX has been increasing and about sixty thousands patients are estimated to be taking MTX for the treatment of RA. The highest efficacy relative to toxicity of MTX is supported by the highest retention rate among current DMARDs. Therefore, most of rheumatologist places MTX as a golden standard of DMARD. Recent RCT data in European and North American countries showed that ACR 20 and 50 responses are ranging from 60 to 70% and from 40 to 50%, respectively. In these clinical trials, MTX was usually started at a dose of 7.5 mg weekly and then increased to 15-20 mg/week if the disease activity was still present since the clinical effect of MTX is related to the dose in the range 5 to 20 mg weekly. However, an upper limit of clinical dose of MTX (Rheumatrex) for RA is set to 8 mg weekly and this is a major problem because the majority of patients with active RA need higher doses for the suppression of arthritis. This matter needs an immediate solution. If MTX would be used aggressively for the early suppression of RA, informed consent regarding MTX dose and side effects including their earlier signs should be obtained, especially when patients are taking more than 8 mg weekly.