Data from intravenous tissue plasminogen activator studies have shown rapidly diminishing clinical benefit beyond 3 hours when noncontrast CT is used for treatment triage. Newer trials, such as the Desmoteplase in Acute Ischemic Stroke trial, have now successfully pushed the time window out to 9 hours using the concept of penumbral imaging and treatment of the perfusion-diffusion mismatch. Advanced imaging with CT or MR imaging protocols is providing a means for rational physiologic selection and outcomes assessment in stroke treatment.