Ischemic stroke (IS) is one of the leading causes of death and neurological disability worldwide. In 2014, we estimate, nearly 1.5 million ischemic strokes occurred in the seven major pharmaceutical markets, and 1.1 million prevalent cases survived a stroke in the previous year. More than 15 years after its approval, recombinant tissue plasminogen activator (rt-PA; alteplase [Genentech’s Activase, Boehringer Ingelheim’s Actilyse, Kyowa Hakko Kirin’s Activacin, Mitsubishi Tanabe Pharma’s Grtpa]) remains the only pharmacological therapy approved for the acute treatment of IS in all markets under study. However, because of strict inclusion criteria and documented safety risks, we estimate the drug was administered to only 7% of diagnosed patients who experienced an IS event in 2014. Given the staggering societal costs of stroke and the historical propensity for pipeline therapeutics to fail in development, there remains a dire need and enormous opportunity for alternative treatments—be they thrombolytic, neuroprotective, or neurorestorative; drugs or devices; acute or recovery—that can safely and effectively prevent permanent neurological damage in a greater percentage of patients during an IS event and help restore lost function for the millions of post-stroke survivors who live with residual impairment.