© 2016 Elsevier B.V. The pharmacotherapy management of cancers of the nervous system has significant overlap with systemic solid cancers that may utilize similar drugs or agents. There is however a unique aspect related to central nervous system (CNS) cancers where therapies directed against a malignant process may have enhanced toxicities or toxicities unique to the CNS. In addition, many agents used to treat CNS malignancies have unique CNS toxicities that may require a specific intervention. This chapter attempts to review conventional and biologic therapies utilized for CNS malignancies and characterize expected and, if known, unique toxicities.