Brainstem gliomas (BSGs) which have extremely poor prognosis represent up to 20% of all pediatric brain tumors, while only for 1-2% of adult brain tumors. Because of high mortality and morbidity rates of biopsy or any surgical excision, treatment decisions are usually based on MRI findings alone and not include a histopathological diagnosis. However, technologic advances in recent years made it possible to surgically approach BSGs with reduced mortality and morbidity, and therefore, surgery became a more commonly practiced treatment modality than before in such patients. Accessible evidence suggest the conventionally fractionated total dose of 54-60 Gy (1.8-2.0 Gy per fraction) RT as the standard of care for BSG patients, however, it should be noted that treatment response is almost always transient and followed by inevitable fatal recurrences. For this reason, studies focusing on molecules that may enhance the effectiveness of RT may potentially play an important role in changing the poor fate of BSG patients, but, this can only be achievable by cooperative studies targeting tumor biology to determine the genetic characteristics and molecular markers of BSG.