The inherent biology of neural stem cells (NSCs) endows them with capabilities that not only circumvent many of the limitations of other gene transfer vehicles, but that enable a variety of novel therapeutic strategies heretofore regarded as beyond the purview of neural transplantation. Most neurodegenerative diseases are characterized not by discrete, focal abnormalities but rather by extensive, multifocal, or even global neuropathology. Such widely disseminated lesions have not conventionally been regarded as amenable to neural transplantation. However, the ability of NSCs to engraft diffusely and become integral members of structures throughout the host CNS, while also expressing therapeutic molecules, may permit these cells to address that challenge. Intriguingly, while NSCs can be readily engineered to express specified foreign genes, other intrinsic factors appear to emanate spontaneously from NSCs and, in the context of reciprocal donor–host signaling, seem to be capable of neuroprotective and/or neuroregenerative functions. Stem cells additionally have the appealing ability to ‘home in’on pathology, even over great distances. Such observations help to advance the idea that NSCs–as a prototype for stem cells from other solid organs–might aid in reconstructing the molecular and cellular milieu of maldeveloped or damaged organs.