Neural stem cells (NSCs) are subscribed extraordinary potential in repair of the damaged nervous system. However, the molecular identity of NSCs has not been established. Most NSC cultures contain large numbers of multipotent, bipotent, and lineage restricted neural progenitors, the majority of which appear to lose neurogenic potential after expansion. This review first discusses the neurogenic to gliogenic switch that is characteristic of progenitor development in vivo and in NSC cultures, and then the cell intrinsic and extrinsic mechanisms regulating the sequential differentiation of neurons and glia. Finally, we discuss potential methods for maintaining the neurogenic potential of NSC cultures after expansion.