The intent of this review was to examine the effects of hyperoxic gas mixtures on human performance. The evidence seems clear that performance is enhanced when O2-enriched gases are inhaled during exercise; however, the physiological mechanisms responsible for the improvement remain obscure. Increased pressure has a detrimental effect on performance, so that studies using hyperbaric oxygenation are ambiguous if the intent is to understand the effects of increased PO2. The large increases in maximal O2 uptake with hyperoxia reported in the literature may be erroneous because of problems encountered with the Douglas bag technique when gases with elevated O2 fractions are used. These apparent increases cannot be easily reconciled with published values for cardiac output and blood gas concentrations during exercise with hyperoxia. The effects of elevated PO2 are apparently widespread and, to a degree, independent; these include effects on pulmonary ventilation, on vascular smooth muscle, and on cellular metabolism. The available data do not lend strong support to the hypothesis that improvement in O2 delivery is responsible for the enhanced performance with hyperoxia. There are effects of hyperoxia on the pulmonary responses to exercise and on the acid-base responses. There is evidence that one or both of these mechanisms could play an important role in the changes in performance with hyperoxia.