Over the last decade, interest in treatment of ischemic stroke has increased significantly. Perhaps the single most important feature of attempts to improve the outcome of stroke patients has been that the interventions be applied within the very early hours of stroke symptoms. This has spawned efforts to understand the vascular and neuronal responses to cerebral artery reperfusion experimentally. Important prospective clinical studies of thrombolysis in acute ischemic stroke have been completed, and large placebo-controlled, symptom-based studies are now underway worldwide. Here, we consider the central features of those studies, their experimental basis, and the future importance of adjunctive therapies to recanalization in focal brain ischemia acutely. Risks and benefits are discussed. This collection benefits from the opinions of experts and workers in this rapidly evolving and exciting field.