Neural stem cells (NSCs) are the main vehicle for genetic and molecular therapies in the central nervous system (CNS). The sustainability of NSCs has been ensured through genetic manipulation both in vitro and in vivo. NSC lines have also been immortalized and controlled for cell growth in similar fashion. Their potential to differentiate and their genetic plasticity make them the modality of choice for cellular transplantation. After transplantation, NSCs also exhibit inherent long-distance migratory capabilities and a remarkable capacity to integrate into brain structures. This makes NSCs the ideal candidate for delivery and expression of therapeutic genes. Mouse models of CNS diseases have already demonstrated the efficacy of such NSC-mediated treatment, and further investigations are underway to bridge the gap into true clinical application. Finally, the imaging possibilities with NSC transplants are endless, and they will be a pivotal component to safe and effective human transplantation. This paper provides an overview on NSCs and the various methods in which they have been genetically manipulated for biological investigation.