Restorative strategies after stroke are focused on the remodeling of cerebral endothelial cells and brain parenchymal cells. The latter, i.e., neurons, neural precursor cells and glial cells, synergistically interact with endothelial cells in the ischemic brain, providing a neurovascular unit whose components can be used as target for stroke therapies. Following focal cerebral ischemia, brain capillary cells are enabled to sprout. Neural precursor cells proliferate and migrate along cerebral microvessels to the ischemic lesion. Glial cells promote the restoration of functional microvessels and at the same time control the buildup of the extracellular matrix, creating a favorable environment to neuronal plasticity both in the ischemic and contralesional brain hemiphere. Until now, a large majority of studies have been performed in young, otherwise healthy animals. Recent behavioral, histochemical and molecular biological studies have shown that restorative brain responses differ between young and old animals, and that they are also modulated by age-related vascular risk factors, i.e., atherosclerosis, diabetes and hyperlipidemia. We claim that age aspects should more carefully be taken into consideration in translational proof-of-concept studies.