Isolated brain tumors contain cells that exhibit stem cell features and a tissue microenvironment bearing remarkable similarities to the normal neurogenic niche. This supports the idea that neural stem (NSCs) or progenitor cells, and their progeny are the likely tumor cell(s) of origin. This prompted the investigation of the relationship between NSCs/progenitors and the initiation of tumorigenesis. These studies led to the identification of common signaling machineries underlying NSC development and tumor formation, particularly those with known roles in proliferation and cell fate determination. This review will explore the molecular mechanisms that regulate NSC behavior in the neurogenic niche of the forebrain, and how deregulation of the developmental potential of NSCs might contribute to tumorigenesis.