The development of a neural stem cell (NSC) treatment for ischemic brain injury would be of great benefit. This review focuses on recent advances in knowledge and practices toward the development of a successful NSC therapy for patients who have experienced stroke. The data supporting potential mechanisms by which somatic stem cells orchestrate neuroprotection, neurogenesis and vascularization, leading to pronounced functional improvements in stroke-induced deficits are critically reviewed. A model is proposed in which the host's immune system plays a central role in stem cell-induced neural repair. In addition, the source of stem cells and the effect of immunosuppression in clinical trials of stem cell therapy are discussed. The beneficial effects of NSCs in animal models of stroke, combined with a consideration of clinical requirements, can potentially provide an effective NSC treatment for patients who have experienced stroke.