Ependymoma is a locally aggressive tumor with metastatic potential that arises in diverse locations throughout the brain and spine in children. Tumor and treatment may result in significant morbidity. Cure remains elusive for many patients owing to diverse biology and resistance to conventional therapy. The implementation of systematic postoperative irradiation in clinical trials during the past 20 years has increased the proportion of patients achieving durable disease control with excellent results, as measured by objective functional outcome measures. Clinical, pathologic, and molecular risk stratification should be used to refine treatment regimens for children with ependymoma to reduce the risk of complications associated with therapy and increase the rate of disease control in the setting of combined modality or more intensive therapy. This review covers standards of care and current clinical trials for children with ependymoma, emphasizing the history and evolution of treatment regimens during the past 20 years and the clinical questions they hoped to address.