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Neural stem cells (NSCs) have been proposed as a promising cellular source for the treatment of diseases in nervous systems. NSCs can self-renew and generate major cell types of the mammalian central nervous system throughout adulthood. NSCs exist not only in the embryo, but also in the adult brain neurogenic region: the subventricular zone (SVZ) of the lateral ventricle. Embryonic stem (ES) cells acquire NSC identity with a default mechanism. Under the regulations of leukemia inhibitory factor (LIF) and fibroblast growth factors, the NSCs then become neural progenitors. Neurotrophic and differentiation factors that regulate gene expression for controlling neural cell fate and function determine the differentiation of neural progenitors in the developing mammalian brain. For clinical application of NSCs in neurodegenerative disorders and damaged neurons, there are several critical problems that remain to be resolved: 1) how to obtain enough NSCs from reliable sources for autologous transplantation; 2) how to regulate neural plasticity of different adult stem cells; 3) how to control differentiation of NSCs in the adult nervous system. In order to understand the mechanisms that control NSC differentiation and behavior, we review the ontogeny of NSCs and other stem cell plasticity of neuronal differentiation. The role of NSCs and their regulation by neurotrophic factors in CNS development are also reviewed.