The human brain contributes 2% of the body weight yet receives 15% of cardiac output and demands a constant supply of oxygen (O2) and nutrients to meet its metabolic needs. Cerebral autoregulation is responsible for maintaining a constant cerebral blood flow that provides the supply of oxygen and maintains the energy storage capacity. We selected oxygen administration-related studies published between 1975–2021 that included meta-analysis, original research, commentaries, editorial, and review articles. In the present narrative review, several important aspects of the oxygen effects on brain tissues and cerebral autoregulation are discussed, as well the role of exogenous O2administration in patients with chronic ischemic cerebrovascular disease: We aimed to revisit the utility of O2administration in pathophysiological situations whether or not being advantageous. Indeed, a compelling clinical and experimental body of evidence questions the utility of routine oxygen administration in acute and post-recovery brain ischemia, as evident by studies in neurophysiology imaging. While O2is still part of common clinical practice, it remains unclear whether its routine use is safe.