Hyperbaric oxygen (HBO) therapy is defined by the Undersea and Hyperbaric Medical Society (UHMS) as a treatment in which a patient intermittingly breathes 100% oxygen under a pressure that is greater than the pressure at sea level [a pressure greater than 1 atmosphere absolute (ATA)]. HBO has been shown to be a potent means to increase the oxygen content of blood and has been advocated for the treatment of various ailments, including air embolism, carbon monoxide poisoning, wound healing and ischemic stroke. However, definitive established mechanisms of action are still lacking. This has led to uncertainty among clinicians, who have understandingly become hesitant in regard to using HBO therapy, even in situations where it could prove beneficial. Therefore, this review will summarize the literature regarding the effects of HBO on brain oxygenation, cerebral blood flow and intracranial pressure in both the healthy and injured brains, as well as discuss how changes in these three factors can impart protection.