Stroke is the third leading cause of morbidity and mortality in the United States, with over 700,000 new occurrences every year. Strokes are typically not acutely lethal. Rather, ~66% of patients survive the initial event, living for an average of seven years. The resulting damage and associated functional deficits may still be profound. Strokes are typically caused by the thromboembolic occlusion of a cerebral artery, which produces focal ischemia. Loss of blood flow to an area of neural tissue leads to cell death—a cerebral infarct. The surrounding tissue remains viable yet vulnerable for several hours, and can die even 24 hours after the initial event. Nonetheless, only one drug is approved by the Food and Drug Administration to treat acute stroke, with limitations to the first three hours after symptoms start. The classical response of the brain to injury involves astrogliosis, macrophage activation and angiogenesis, activated in part by the release of fibroblast growth factor (FGF) 2, higher levels of which are associated with better patient prognoses. FGF2 must form a head-to-head dimer, binding to heparan sulfate in such a way as to maintain direct FGF-FGF contact. Dimerized fibroblast growth factor 2 (dFGF2) is a novel engineered protein consisting of two monomers of FGF2 joined by a tripeptide linker, putting the monomers in optimal conformation to interact with high-affinity FGF receptors and to promote a cellular response. This engineered version of FGF2 is stable in the active conformation, independent of heparans in the extracellular matrix for maximal activity, and can even achieve greater biological effects than the monomer both in vitro and in vivo. The potential utility of dFGF2 in stroke was also investigated. Intracisternal and intravenous administration of dFGF2 enhance sensorimotor and vestibulomotor recovery after 28 days in rat models of focal cerebral infarction when dFGF2 is administered greater than 24 hours after the induction of ischemia. The effects of dFGF2 are likely due to increased angiogenesis, plasticity and induced stem cell differentiation. The robust recovery induced by dFGF2 in over 500 rats validates this engineered growth factor as a potential stroke treatment, worthy of clinical trials.