Despite the success of acute reperfusion therapies for the treatment of acute ischemic stroke, only a minority of patients receive such treatment. Even patients who receive reperfusion therapy remain at risk for further neuronal death through progressive infarction and secondary injury mechanisms. The goal of neurocritical care for the patient with acute ischemic stroke is to optimize long-term outcomes by minimizing the amount of brain tissue that is lost to these processes. This is accomplished by optimizing brain perfusion, limiting secondary brain injury, and compensating for associated dysfunction in other organ systems. Because of the rapid and irreversible nature of ischemic brain injury, it is crucial for best neurocritical care practices to begin as early as possible. Therefore, this chapter will discuss optimal, pragmatic neurocritical care management of patients with acute ischemic stroke during the “golden” emergency department hours from the perspective of the neurointensivist. Major topics include cerebral perfusion optimization; management of cerebral edema; post-thrombolytic care; acute anticoagulation; treatment of commonly associated cardiac and pulmonary complications; fluid, electrolyte and glucose management; the role of induced normothermia and therapeutic hypothermia; and prophylaxis against common complications.