Reperfusion strategies such as vascular thrombolysis and thrombectomy are the first-line treatments recommended for acute ischemic stroke. However, only half of these patients achieve functional independence after endovascular reperfusion of large vessel occlusions. Timely restoration of blood flow is crucial, but not all reperfusion results in benefit, a phenomenon termed futile reperfusion. Futile reperfusion occurs when brain tissue has already suffered irreversible damage before reperfusion or when other factors undermine the benefits of restored blood flow. These factors include reperfusion-not rescued injury, reperfusion-induced injury, and the no-reflow phenomenon. The success of reperfusion therapies also hinges on timing and tissue condition after stroke. Defining these time and tissue windows more precisely could refine stroke interventions, potentially expanding effective reperfusion opportunities tailored to individual patients, thereby reducing the incidence of futile reperfusion. This perspective article delves into the complexities of futile reperfusion and the critical roles of time and tissue windows in determining stroke outcomes.