Hyperoxia, or excess oxygen supplementation, prevails in the intensive care unit (ICU) without a beneficial effect and, in some instances, may cause harm. Recent interest and surge in clinical studies in mechanically ventilated critically ill patients has brought this to the attention of clinicians and researchers. Hyperoxia can cause alveolar injury, pulmonary edema, and subsequent systemic inflammatory response and is known to augment ventilator-associated lung injury. Liberal oxygenation practices are also associated with increased mortality in subsets of critically ill patients with post-cardiac arrest, stroke, and traumatic brain injury. Most clinicians agree that oxygen titration should be done and, with appropriate safeguards, lower oxygenation targets may be acceptable and possibly beneficial in many critically ill patients. However, this problem is often overlooked. The use of periodic reminders and decision support may facilitate implementation of more precise oxygen titration at the bedside of critically ill patients. For implementing practice change, studies involving education and guidance of all health care staff involved in oxygen management are critical.