ICU-ROX tested whether mechanically ventilated adults should receive a conservative oxygen strategy that limited exposure to high inspired oxygen concentrations compared with usual oxygen therapy. The trial included 1,000 critically ill adults expected to require mechanical ventilation beyond the first day. The conservative strategy reduced exposure to oxygen in some patients, but it did not significantly increase ventilator-free days or produce a clear mortality benefit. The findings are important because excessive oxygen can cause oxidative injury, yet the ideal oxygen target in critical illness is not defined simply by “lower is always better.” The study supports a more measured approach: clinicians should avoid unnecessary hyperoxia while maintaining adequate oxygen delivery and considering the underlying disease. Oxygen targets may need to differ in ARDS, cardiac arrest, traumatic brain injury, COPD and other conditions. ICU-ROX also demonstrates the difficulty of translating physiologic concerns into universally beneficial treatment thresholds. The practical takeaway is to treat oxygen like a drug—titrate it to a clinically meaningful target and reassess frequently rather than leaving high FiO2 settings unchanged. The trial therefore complements, rather than replaces, disease-specific evidence and reinforces the need for individualised oxygen therapy.