The supplemental oxygen administration is a common therapeutic intervention in the management of patients with arterial hypoxemia, in order to improve tissue hypoxia and maintain aerobic metabolism. Unfortunately the therapeutic use of high concentration of FiO2 for a prolonged period of time causes anatomic and functional damage to the lungs similar to that described in Acute Respiratory Distress Syndrome (ARDS). The aim of the study is to review the data from recent about oxygen toxicity mechanisms - which is a biochemical paradox since oxygen is simultaneously essential for aerobic metabolism - and to understand of the cellular and molecular mechanisms that finally cause the cellular damage and death. This is a field for future research about the oxygen caused damage and the final goal is the investigation of new therapeutic approaches to confront and minimize the hyperoxia induced problems. Pneumon 2004, 17(1):18-28.