Neurosurgical management of malignancy is a broad field that relies on collaboration between many medical disciplines. Malignant tumors of the central nervous system often require a multifaceted management approach, owing not only to their inherently sensitive nature but also because in many cases, curative treatments have yet to be established. In this chapter, we begin with a discussion of several characteristic high-grade malignancies in neurosurgery, including some brief epidemiology and recent prognostic data. We will then review the central role of resection and biopsy. Secondarily, we cover the current state of adjuvant and postoperative treatments, including radiation, chemotherapy, molecular therapies, immunotherapy, and targeted treatments. Finally, we discuss how successful care for patients afflicted with high-grade brain or spinal cord malignancies hinges on the integration of multiple medical specialties and the entire care team.