Treatment with low-dose methotrexate (MTX) is an important element in the therapy of juvenile idiopathic arthritis (JIA). It could be demonstrated in placebo-controlled trials that MTX is a safe and effective drug which is generally well tolerated by children and adolescents. MTX is usually used at a dose of 10-15 mg/m(2)/week, whereby oral administration is preferred for children. Side effects occur mainly in the form of gastro-intestinal discomfort such as nausea and vomiting or raised transaminases, which can be effectively treated with folic-acid supplementation.There are no general recommendations to date regarding in particular duration and discontinuation of MTX treatment or combination treatment with other disease-modifying antirheumatic drugs or biologics. These unresolved questions are the subject of current trials in which biomarkers have an increasingly important role.