A decade long focus on neuroprotection for stroke and neural injury, and its failure to translate into the clinical setting has led to a major shift of focus from neuroprotection to neurorestoration. Neurorestoration involves the remodeling and rekindling of neurovascular plasticity within the central nervous system which drive neurological recovery. Bone marrow-derived mesenchymal stem cell (BMSC) therapy is a promising cell-based neurorestorative therapy for stroke. This chapter provides an update on the use of BMSCs to promote neurorestorative effects in the sub-acute and chronic phases after stroke. The biological processes involved in promoting neurorestorative effects post ischemia are outlined, molecular mechanisms that promote neurogenesis, synaptogenesis, vascular and white matter remodeling, and neurovascular interactions and plasticity are discussed, the involvement of microRNA’s in regulating neurorestorative mechanisms is introduced, and an update on clinical trials for BMSC treatment of stroke is presented.