This study discusses the use of chimeric antigen receptor (CAR) T cell therapy to treat pediatric central nervous system (CNS) tumors. These tumors are the most common solid malignancy in children, and CAR T cell therapy has shown success in treating childhood leukemia and preclinical efficacy against pediatric CNS tumors. However, delivering CAR T cells to tumors in the brain and spine is challenging, as T cells have difficulty reaching these sites. To address this challenge, locoregional CAR T cell delivery via infusion through an intracranial catheter is being studied in early phase clinical trials. Here, we describe Seattle Children's experience in preparing for and delivering intracranial T cell infusions, and the safety of the procedure based on 307 intracranial CAR T cell doses. This research offers hope for improving outcomes for recurrent CNS tumors and universally fatal diseases like diffuse intrinsic pontine glioma (DIPG).