While the time window for reperfusion after ischemic stroke continues to increase, many patients are not candidates for reperfusion under current guidelines that allow for reperfusion within 24 h after last known well time; however, many case studies report favorable outcomes beyond 24 h after symptom onset for both spontaneous and medically induced recanalization. Furthermore, modern imaging allows for identification of penumbra at extended time points, and reperfusion risk factors and complications are becoming better understood. Taken together, continued urgency exists to better understand the pathophysiologic mechanisms and ideal setting of delayed recanalization beyond 24 h after onset of ischemia.