Nervous system tumors represent unique neoplasms that arise within the central and peripheral nervous system. Recent progress in generating genetically engineered mouse models of these tumors has advanced our understanding of the critical molecular and cellular events important for the development of these tumors. Recently, the National Cancer Institute-sponsored Mouse Models of Human Cancer Consortium convened a meeting on Nervous System Tumors to review recent advances and suggest directions for future research. Refined and novel approaches to modeling central nervous system tumors, including gliomas, meningiomas, medulloblastomas, and oligodendrogliomas, as well as peripheral nervous system tumors such as neurofibromas, schwannomas, and malignant peripheral nerve sheath tumors, were presented. In this review, we discuss the current status of mouse modeling of human nervous system cancers with a specific focus on unresolved scientific questions pertaining to the molecular genetics and cellular biology of these tumors.