The interaction between glycemic control and critical neurologic illness and injury is complex. Hyperglycemia can be either the cause or the result of severe brain injury. Hyperglycemia in acute neurologic injury is associated with worse neurologic outcomes. Demographic patterns, including an aging population and shifts in racial and ethnic representation, contribute to the increasing prevalence of hyperglycemia and diabetes among victims of the most common neurologic emergencies. This article reviews the epidemiology of the problem, relevant pathophysiology, the use of tight glycemic control therapy in other populations, and the potential for tight glycemic control as a way to improve outcomes after acute neurologic illness and injury.