Mechanical ventilation is required frequently for patients with neurologic disorders for airway protection, pulmonary insufficiency, or management of intracranial pressure. Patients with neurologic disease are prone to hypoventilation, hypoxia, aspiration, atelectasis, and lung collapse. This chapter presents a case study of a 55-year-old female with sudden onset of severe headache and deterioration in her level of consciousness. Mechanical ventilation mode was switched to pressure control ventilation, and positive end expiratory pressure (PEEP) incrementally increased to 15cm H2O with improvement in both oxygenation and ventilation. Upon postintubation, both her mental status and respiratory status gradually improved. The chapter discusses the modes and complications of mechanical ventilation in patients with neurologic disorders. Patients with neurologic illness often require intubation and mechanical ventilation secondary to decreased levels of consciousness, impaired airway protection, neuromuscular weakness, or pulmonary complications. Mechanical ventilation strategies require optimizing oxygenation and ventilation with respect to the particular neurologic disorder.