Therapeutic strategies for brain repair by stem cells. For brain repair in regions outside of the germinal centers, such as the cerebral cortex, stem cells may contribute to repair through recruitment or replacement. In the case of recruitment (a), the environment in the non-neurogenic region must be enhanced with appropriate environmental signals to attract endogenous neural stem cells, possibly from the germinal centers, to expand this population of cells, and to instruct their differentiation into appropriate neurons. This environmental enhancement could most likely be achieved using in vivo gene therapy leading to transgene expression by endogenous cells and may require a precise temporal and spatial delivery of appropriate transgenes to achieve the desired outcome. In the case of replacement (b), neural stem cells derived from embryonic, fetal, or adult sources could be expanded in vitro, directed down specific neuronal lineages, and genetically modified to express the necessary environmental signals. Thus committed to the correct phenotype and expressing necessary environmental signals to ensure their survival, these cells could then be grafted to the target region. Alternatively (c), the environment could be enhanced by gene delivery before (or possibly after) the grafting of the replacement neural stem cells.