Important advances in our understanding of the molecular biology of brain tumors have resulted in a rapid evolution in the taxonomy of central nervous system (CNS) tumors, which culminated in the revised 2016 World Health Organization classification of CNS tumors that incorporates an integrated molecular/histologic diagnostic approach. Our expanding understanding of brain tumor genomics and molecular evolution during the disease course has started to impact clinical management. Furthermore, incorporation of genomic information in ongoing and planned neuro-oncology clinical trials is expected to lead to improved outcomes and result in personalized treatment options for patients with CNS malignancies.