Acute ischemic stroke is a leading cause of morbidity and mortality in the United States, and a majority of acute ischemic stroke patients are evaluated for the first time by a clinician in the emergency department. Intravenous tissue plasminogen activator and mechanical thrombectomy are powerful tools for the treatment of acute ischemic stroke. Treatment algorithms for acute ischemic stroke are evolving rapidly, and strokes in select patients can now be treated up to 24 hours after last known well time. However, even in the setting of extended treatment times, the treatment effects of both intravenous tissue plasminogen activator and mechanical thrombectomy are time dependent. The emergency clinician must remain current with the newest treatment algorithms in order to provide expeditious and high-quality care to stroke patients.