OBJECTIVES: A narrative review of the pathophysiology linking altered airway pressure and intracranial pressure and cerebral oxygenation. DATA SOURCES: Online search of PubMed and manual review of articles (laboratory and patient studies) of the altered airway pressure on intracranial pressure, cerebral perfusion, or cerebral oxygenation. STUDY SELECTION: Randomized trials, observational and physiologic studies. DATA EXTRACTION: Our group determined by consensus which resources would best inform this review. DATA SYNTHESIS: In the normal brain, positive-pressure ventilation does not significantly alter intracranial pressure, cerebral oxygenation, or perfusion. In injured brains, the impact of airway pressure on intracranial pressure is variable and determined by several factors; a cerebral venous Starling resistor explains much of the variability. Negative-pressure ventilation can improve cerebral perfusion and oxygenation and reduce intracranial pressure in experimental models, but data are limited, and mechanisms and clinical benefit remain uncertain. CONCLUSIONS: The effects of airway pressure and ventilation on cerebral perfusion and oxygenation are increasingly understood, especially in the setting of brain injury. In the face of competing mechanisms and priorities, multimodal monitoring and individualized titration will increasingly be required to optimize care.