© 2017 The Author(s). Background: Methotrexate is the most commonly used disease modifying antirheumatic drug in the treatment of juvenile idiopathic arthritis and can be effective in controlling disease in many patients. Main body: A significant proportion of patients experience nausea and vomiting induced by methotrexate therapy, which can lead to decreased quality of life and discontinuation of treatment with methotrexate. Many strategies have been employed in attempts to reduce methotrexate-induced nausea, including folate supplementation, switching from oral to subcutaneous methotrexate, anti-emetic therapy, behavioral therapy, and others. Anticipatory nausea can be difficult to treat, making primary prevention of nausea with anti-emetics an attractive approach. Conclusion: Understanding the prevalence and impact of methotrexate-induced nausea, as well as potentially effective interventions, may help maximize the therapeutic benefits of methotrexate.