Acute ischemic stroke (AIS) is a serious neurological disease. Normobaric hyperoxia (NBHO) is both a non-invasive and easy method that seems to be able to improve outcomes after cerebral ischemia/reperfusion. In clinical trials, normal low-flow oxygen has been shown to be ineffective, but NBHO has been shown to have a transient brain-protective effect. Today, NBHO combined with recanalization is the best treatment available. NBHO combined with thrombolysis is considered to improve neurological scores and long-term outcomes. Large randomized controlled trials (RCTs), however, are still needed to determine the role they will have in stroke treatment. RCTs of NBHO combined with thrombectomy have both improved infarct volume at 24 hours and the long-term prognosis. These two mechanisms most likely play key roles in the neuroprotective actions of NBHO after recanalization, including the increase in penumbra oxygen supply and the integrity of the blood-brain barrier (BBB). Considering the mechanism of action of NBHO, oxygen should be given as early as possible to increase the duration of oxygen therapy before recanalization is initiated. NBHO can further prolong the existence time of penumbra, so that more patients may benefit from it. Overall, however, recanalization therapy is still essential.