Gliomas have been treated by a specialized team including neurosurgery, radiation therapy, and neuro-oncology, as well as depending on integrated sophisticated facilities and multi-professional team. Despite these huge efforts to glioma treatment, glioblastoma, one of the most frequent gliomas, has median life expectance for just 15 months, so these results are still an unmet need. Related to the systemic treatment, some cancer approaches have been revolutionized with new strategies, such as immunotherapy, although in neuro-oncology, this alternative still has challenges to overcome. Throughout this chapter, relevant information and key points will be discussed to the best way to manage systemic treatment and improve glioma overall survival.