Early treatment of ischemic stroke with thrombolytics is associated with improved outcomes, but few stroke patients receive thrombolytic treatment in part due to the 3-hour time window. Advances in neuroimaging may help to aid in the selection of patients who may still benefit from thrombolytic treatment beyond conventional time-based guidelines. In this article the authors review the available literature in support of using advanced neuroimaging to select patients for treatment beyond the 3-hour time window cutoff and explore potential applications and limitations of perfusion imaging in the treatment of acute ischemic stroke.