Neurofibromatosis type 1 (NF1) patients are complex and present for a variety of neurosurgical interventions. The most typical manifestations are multiple neurofibromas and melanogenic abnormalities (both of neural crest origin), but the phenotype may also include skeletal abnormalities. This chapter presents a case study of a 39-year-old female with a history of NF1 and four previous spine surgeries, the last of which occurred at the age of 16. It results from a mutation of the NF1 gene on chromosome 17, which encodes the tumor suppressor neurofibromin. Patients with NF1 may present for surgical procedures involving peripheral nervous system tumors (neurofibromas, malignant peripheral nerve sheath tumors), central nervous system tumors (benign optic gliomas, astrocytomas), scoliosis or other skeletal abnormalities, and a host of other disorders. Given the multisystem involvement and variable phenotype, a systematic approach to the NF1 patient is necessary for safe perioperative care.