A number of developmental cues underlie proper brain morphogenesis and plasticity. Hedgehog (Hh) signaling pathway plays a critical role in determining proper embryonic patterning and cell fate determination in the central nervous system. Embryonic and adult neural progenitor cells are mostly responsive to Hh signaling, thereby sustaining developmental and tissue repair processes. Hh signaling pathway is finely tuned in order to maintain physiological cell functions during the development of the nervous system and afterwards. Its deregulation is responsible for a number of diseases (e.g. cancer, neurodegenerative disorders). Recently identified Hh pathway regulatory signals involved in the maintenance of nervous tissue shape and their relevance in human pathology are discussed here.