The discovery of a Sonic Hedgehog (Shh) signaling pathway in the mature vertebrate CNS has paved the way to the characterization of the functional roles of Shh signals in normal and diseased brain. Shh is proposed to participate in the establishment and maintenance of adult neurogenic niches and to regulate the proliferation of neuronal or glial precursors in several brain areas. Consistent with its role during brain development, misregulation of Shh signaling is associated with tumorigenesis while its recruitement in damaged neural tissue might be part of the regenerating process. This review focuses on the most recent data of the Hedgehog pathway in the adult brain and its relevance as a novel therapeutic approach for brain diseases including brain tumors.