Several congenital syndromes caused by germline mutations in tumor suppressor genes predispose to the development of glial tumors. In the last few decades our knowledge about the molecular functions of these genes and the pathogenesis of hereditary tumor syndromes has greatly increased. The most common syndromes are the neurofibromatoses (type 1 and type 2) and the tuberous scleroses complex. There are interesting overlaps in the molecular pathogen-esis. Deregulation of Ras or downstream Ras pathways including MEK/ERK and AKT/ mTOR plays an important role in these three syndromes. Other rare syndromes include Li-Fraumeni, melanoma-astrocytoma, and Turcot syndrome involving cell cycle regulators and DNA repair genes. The genes and pathways involved in the pathogenesis of these syndromes also play an important role in the development of sporadic tumors. Therefore research on hereditary syndromes contributes substantially to our understanding of tumor formation.