The importance of the trace element selenium for human health is well established. Selenium plays a central role in the formation of selenocysteine, a modified amino acid located in the catalytic center of selenoenzymes. The crucial role of selenium in these enzymes revolves around the maintenance of many redox systems in cellular and extracellular compartments. In addition, selenium plays an important role in thyroid hormone metabolism. Several clinical trials of selenium supplementation in critically ill patients have been conducted to date, providing an interesting and provoking mix of findings. Despite some promising results, no definitive answers regarding the effects of selenium supplementation on critically ill patient mortality or morbidity exist. Further research in the setting of well-designed, prospective, randomized trials is necessary to better define the role of selenium supplementation in critically ill patients.