The astonishing progress in the field of stem cell biology during the past 40 years has transformed both science and medicine. Neural stem cells (NSCs) are the stem cells of the nervous system. During development they give rise to the entire nervous system. In adults, a small number of NSCs remain and are mostly quiescent; however, ample evidence supports their important roles in plasticity, aging, disease, and regeneration of the nervous system. Because NSCs are regulated by both intrinsic genetic and epigenetic programs and extrinsic stimuli transduced through the stem cell niche, dysregulation of NSCs due to either genetic causes or environmental impacts may lead to disease. Therefore, extensive investigations in the past decades have been devoted to understanding how NSCs are regulated. On the other hand, ever since their discovery, NSCs have been a focal point for cell-based therapeutic strategies in the brain and spinal cord. The limited number of NSCs residing in the tissue has been a limiting factor for their clinical applications. Although recent advancements in embryonic and induced pluripotent stem cells have provided novel sources for NSCs, several challenges remain. In this special issue, leaders and experts in NSCs summarize our current understanding of NSC molecular regulation and the importance of NSCs for disease modeling and translational applications.