Ventilating patients with elevated oxygen tensions alters normal respiratory physiology and may damage lung tissue, depending on coexisting host and iatrogenic factors. Pulmonary oxygen toxicity begins at a cellular level when the generation of reduced oxygen intermediates exceeds local defenses. The mainstay of therapy is prevention. Supplemental oxygen should be prescribed at the lowest concentration possible that will still allow adequate tissue oxygenation. Presently, no specific therapeutic interventions are approved for use in humans to treat pulmonary oxygen toxicity. New agents that act as free radical scavengers or reduce free radical formation may prove useful in future clinical trials based on many of the scientific studies summarized in this review.