Hypothermia is a promising therapeutic option for stroke patients and an established neuroprotective treatment for global cerebral ischemia after cardiac arrest. While whole body cooling is a feasible approach in intubated and sedated patients, its application in awake stroke patients is limited by severe side effects: Strong shivering rewarms the body and potentially worsens ischemic conditions because of increased O2 consumption. Drugs used for shivering control frequently cause sedation that increases the risk of aspiration and pneumonia. Selective brain cooling by intraarterial cold infusions (IACIs) has been proposed as an alternative strategy for patients suffering from acute ischemic stroke. Preclinical studies and early clinical experience indicate that IACI induce a highly selective brain temperature decrease within minutes and reach targeted hypothermia 10 to 30 times faster than conventional cooling methods. At the same time, body core temperature remains largely unaffected, thus systemic side effects are potentially diminished. This review critically discusses the limitations and side effects of current cooling techniques for neuroprotection from ischemic brain damage and summarizes the available evidence regarding advantages and potential risks of IACI.