The discovery of ionizing radiation’s utility for therapy in cancer heralded a new era in oncology. Application of ionizing radiation in childhood cancer showed great promise in potentiating cure, but compromises in childhood growth, development, and function were quickly noted. As a result alternative modes of delivery were quickly sought out, and some of these modalities are still under prospective evaluation. Given that the potential curative advantages of radiation therapy in children are well known, the metrics for clinical trials in children are now focused on treatment-related adverse events. Here we review the evolution of treatment modalities in childhood cancer, metrics for evaluation, and current therapeutic clinical workflow.