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This study reviews important nutrients responsible for oxidant–antioxidant balance in trauma patients requiring admission to the ICU and rationale for repletion of antioxidants using pharmaconutrition.Oxidative stress is an underlying cause of critical illness due to oxidant–antioxidant imbalance. Multiple nutrients important to oxidative balance have been studied, yet much variety exists among the dosing, timing, and route of administration. Conflict also exists regarding the benefits of particular single nutrients and the effects of combination therapy. Anticipated results of the Reducing Deaths due to Oxidative Stress trial hope to provide further insight to the use of antioxidants in critically ill patients.The goal of this review, though not exhaustive, serves to highlight recent significant studies regarding antioxidant use in the ICU setting while calling for sufficiently powered randomized, controlled trials to elucidate appropriate guidelines for antioxidant administration in regards to ideal dosing, route of administration, timing of administration, duration of therapy, and the role of single versus combination supplementation.