Vitamin D deficiency and its adverse skeletal sequelae are well recognized in the general population. Recent observation of high prevalence of low vitamin D states and their associations with worse clinical outcomes in critically ill populations have sparked interest in the role of supplementation for these patients. High-dose vitamin D efficaciously increases serum levels, but its impact on clinical outcome has not been examined. This article will review results from observational studies on prevalence and outcomes of hypovitaminosis D in critically ill patients, as well as caveats of vitamin D interventional trials. Improved understanding of vitamin D metabolism in critical illness will clarify the therapeutic potential of this pleiotropic hormone and facilitate implementation of cost-effective clinical trials.