Mechanical ventilation has evolved greatly over the last half century, guided primarily by improved comprehension of the relevant pathology/physiology. Neurosurgical patients are a unique subgroup of patients who heavily use this technology for both support, and less commonly, as a therapy. Such patients demand special consideration with regard to mode of ventilation, use of positive end-expiratory pressure, and monitoring. In addition, meeting the ventilatory needs of neurosurgical patients while minimizing ventilatory-induced lung damage can be a challenging aspect of care.