The initial treatment of patients with acute ischemic stroke (AIS) focuses on rapid recanalization, which often includes the use of endovascular therapies. Endovascular treatment depends upon micronavigation of catheters and devices into the cerebral vasculature, which is easier and safer with a motionless patient. Unfortunately, many stroke patients are unable to communicate and sufficiently cooperate with the procedure. Thus, general anesthesia (GA) with endotracheal intubation provides an attractive means of keeping the patient comfortable and motionless during a procedure that could otherwise be lengthy and uncomfortable. However, several recent retrospective studies have shown an association between GA and poorer outcomes in comparison with conscious sedation for endovascular treatment of AIS, though prospective studies are lacking. The underlying reasons why GA might produce a worse outcome are unknown but may include hemodynamic instability and hypotension, delays in treatment, prolonged intubation with or without neuromuscular blockade, or even neurotoxicity of the anesthetic agent itself. Currently, the choice between GA and conscious sedation should be tailored to the individual patient, on the basis of neurologic deficits, airway and hemodynamic status, and treatment plan. The use of institutional treatment protocols may best support efficient and effective care for AIS patients undergoing endovascular therapy. Important components of such protocols would include parameters to choose anesthetic modality, timeliness of induction, blood pressure goals, minimization of neuromuscular blockade, and planned extubation at the end of the procedure.