The past 40 years have seen the evolution of acute ischemic stroke management from unproven therapies du jour, such as steroids, heparin for stroke in evolution, and hypervolemic-hemodilution, to more of a scientific basis for our decision-making process. This evolution is directly related to the advancements in imaging of stroke. It is also related to carefully designed, controlled clinical trials of potential therapies, which have led to the recognition of the benefits of thrombolytic therapy in the acute setting but have also caused confusion and frustration over the lack of benefit for potential neuroprotective agents that once seemed promising.