Several central nervous system (CNS) tumors have a genetic basis. Most individuals will harbor a germline mutation in a cancer-related gene. Although these cancer predisposition syndromes are rare, they pose significant clinical and psychological challenges to the patient and the treating clinician. Over the last years, advances in genetics and biology have enabled a better understanding of the molecular pathways that govern these conditions and have led to the development of novel therapeutic modalities. In this chapter, we summarize the main characteristics of each major hereditary CNS tumor syndrome, and we summarize the main progress made in their diagnosis and management.