The advent of molecular biology has provided tools to delineate genetic mutations that cause disease. Recently, several genetic mutations have been associated with intramedullary spinal cord tumors. Concurrently, advances in micro-neurosurgical techniques have significantly decreased the morbidity of surgical resection. In this review, we describe the current understanding of genetic mutations in sporadic and familial intramedullary spinal cord tumors. The future success of innovative gene therapy protocols may depend upon establishing a cause and effect relationship between these genetic mutations and disease progression. Successful gene therapy will also depend upon increasing the efficiency of gene therapy vector delivery.