Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is thought to affect 1780000 patients in USA and Europe. Its incidence is increasing rapidly in Asia. Drugs with proven clinical activity that are currently used in UC patients include salicylates, steroids, azathioprine and infliximab. None of them is active in every patient and all carry significant side effects. There is a need for other active drugs in UC. Low dose methotrexate has been used for decades in psoriasis, rheumatoid arthritis and Crohn's disease. In these diseases, it is an active, well tolerated and cheap drug. In UC there have been several open series, most of which are retrospective. Overall, these studies have shown promising results, with response rates of 50 to 72 %. There have been two randomized clinical trials of methotrexate vs. placebo in UC. Both were negative but methotrexate was prescribed orally at suboptimal doses. So far, there is no evidence for the efficacy of methotrexate in UC. Therefore, there is a need for clinical trials with methotrexate using adequate dosage and the parenteral route. Two multicenter randomized trials of methotrexate 25 mg/week parenterally vs. placebo are either ongoing (METEOR, the European trial) or being built up (MERIT, the US trial). These trials should determine if methotrexate is a valuable therapeutic option in UC.