Neural stem cells (NSCs) play vital roles in the development and maintenance of brain tissues throughout life. They can also potentially act as powerful sources of regeneration and repair during pathology to replace degenerating cells and counteract deleterious changes in the tissue microenvironment. However, both aging and neurodegeneration involve an up-regulation of processes, such as oxidative stress, inflammation, somatic mutations, and reduction in growth factors in neural tissues, which threaten the robust functioning of NSCs. Nevertheless, recent evidence also indicates that NSCs may possess the intrinsic capability to cope with such stressors in their microenvironment. Whereas the mechanisms governing the responses of NSCs to stress are diverse, a common theme that is emerging suggests that underlying changes in intracellular redox status are crucial. Here we discuss such redox-based regulation of NSCs, particularly in relation to nuclear erythroid factor 2-like 2 (Nrf2), which is a key cellular stress resistance factor, and its implications for successfully harnessing NSC therapeutic potential towards developing cell-based therapeutics for nervous system disorders.