Pediatric brain tumors are most common cancers in childhood and among the leading causes of death in children. Chemotherapy has been used as adjuvant (i.e. after) or neoadjuvant (i.e. before) therapy to surgery and radiotherapy for the management of pediatric brain tumors for more than four decades and gained more attention in the recent two decades. Although chemotherapy has demonstrated its effectiveness in the management of some pediatric brain tumors, failure or inactiveness of chemotherapy is commonly met in the clinics and clinical trials. Some of these failures might be attributed to the blood-brain barrier (BBB), limiting the penetration of systemically administered chemotherapeutics into pediatric brain tumors. Therefore, various strategies have been developed and used to address this issue. Herein, we review different methods reported in the literature to circumvent the BBB for enhancing the present of chemotherapeutics in the brain to treat pediatric brain tumors.