Intravenous thrombolysis is the cornerstone of acute ischemic stroke treatment. However, the benefits of recanalization and reperfusion must be balanced against the risk of intracranial hemorrhage. Time from symptom onset was previously the most important selection tool for identifying patients who would benefit from treatment without prohibitive risk for secondary hemorrhage. Enhanced techniques in noncontrast computed tomography followed by computed tomography and magnetic resonance perfusion imaging led to the expansion of treatment eligibility for intravenous thrombolysis. Perfusion imaging allows for more precise evaluation of tissue at-risk to identify patients who would benefit from treatment many hours beyond symptom onset.