MTX is used in the treatment of several childhood cancers and has side effects of varying severity [1]. Neurotoxicity can occur in up to 15% of patients receiving high-dose MTX [2, 3]. Elevated homocysteine in CSF are documented in such cases. Dextromethorphan, an NMDA receptor antagonist, suppresses homocysteine activity and is the initial treatment. Ketamine, also an NMDA receptor antagonist, may be considered as an optimal treatment choice in intubated patients requiring sedation. We describe the use of ketamine in a pediatric patient with methotrexate-induced neurotoxicity. Ketamine as treatment of MTX-induced neurotoxicity has not been described in the literature.