Abstract The therapeutic landscape of the management of low- and high-grade infiltrating gliomas continues to evolve. Daily clinical decision making in neuro-oncology clinics across the US is frequently challenging, especially for anaplastic and low grade primary brain tumors. The focus of this review is centered on treatments which are approved by the FDA and/or featured in the NCCN Guidelines. Systemic therapy trials using a variety of agents such as temozolomide, bevacizumab, and procarbazine, lomustine, vincristine (PCV), and lastly trials of local therapies including surgical trials using carmustine impregnated wafers as well as trials investigating the administration of tumor treating fields are evaluated. Pivotal trials on the treatment of the primary brain tumors are discussed in detail along with associated correlative studies.