High-grade gliomas and diffuse brainstem gliomas carry a very poor prognosis despite current therapies, and account together for the largest number of deaths in children with brain tumors. Many of these tumors have been found to overexpress the EGF receptor (EGFR). Nimotuzumab (h-R3) is a humanized monoclonal antibody against the EGFR, and consequently inhibits tyrosine kinase activation. In vitro and in vivo studies have supported the antiproliferative, antiangiogenic, pro-apoptotic and radiosensitizing activities of nimotuzumab. Emerging trials suggest a promising role for nimotuzumab as a therapeutic agent in patients with high-grade gliomas. This review attempts to provide a context for the evolving interest and evidence for nimotuzumab in pediatric glioma.