Methotrexate is an immunosuppressive agent used for the management of ocular inflammatory diseases and rheumatic diseases. Despite its use for ocular inflammation, including uveitis, since 1965, the exact efficacy of methotrexate has not been confirmed by a randomized clinical trial thus far. Our review of previous data of treatment outcomes suggested that methotrexate is moderately effective in suppressing ocular inflammation and decreasing corticosteroid use. In addition, methotrexate is relatively safe and well tolerated by most patients and is the most widely used immunosuppressive drug for the treatment of uveitis in children. In addition to systemic administration of the drug, intraocular administration of methotrexate can be a promising treatment option for uveitis.