Mechanical ventilation (MV) is fundamental to the resuscitation of brain injured patients, facilitating tissue oxygen delivery, helping to modulate cerebral vascular reactivity, and ensuring protection of the airway. These benefits come at a cost, which includes a significantly increased risk of pneumonia, delirium, and the complications of sedation and of endotracheal intubation. MV exerts effects on intracranial pressure and cerebral perfusion pressure which may be detrimental in patients with intracranial hypertension. MV can also induce alveolar damage in susceptible individuals, yet changes in ventilation designed to limit this damage may not be tolerated in the setting of brain injury. Recent research has begun to clarify key questions regarding the pathophysiology and management of MV in critically ill neurological patients.