Acute ischemic stroke is a neurological emergency that requires ultra-rapid intervention. Stroke teams and stroke protocols can be devised to expediate evaluation and treatment. In carefully selected patients, thrombolytic therapy offers a significant benefit but must be initialized within 3 hours of stroke onset. Emerging alternative strategies for reperfusion and neuroprotection must also be initiated during the hyperacute period. The role of more traditional therapies, such as antiplatelet agents and anticoagulants, have been better defined through several recent major clinical trials.