Stem cells have been proposed as a new form of cell-based therapy in a variety of disorders, including acute and degenerative brain diseases. Endogenous neural stem cells (eNSCs) have been identified in the central nervous system where they reside largely in the subventricular zone and in the subgranular zone of the hippocampus. eNSCs are capable of self-renewal and differentiation into functional glia and neurons throughout life. However, spontaneous brain regeneration does not suffice to induce significant behavioral improvement in acute or chronic brain injury. Nevertheless, eNSCs responses can be considerably increased by tweaking the pathways governing cell proliferation, migration and differentiation. Contemporary evidence now suggests that such perturbations may lead to better functional outcome after brain injury.