 The therapeutic potential of vitamin D is a topic of intense interest. A high prevalence of low vitamin D levels has been confirmed in patients who are critically ill. Vitamin D deficiency is associated with higher infection rates, 30-day mortality and in-hospital mortality in adult critically ill patients. During critical illness, vitamin D supplementation has a favorable safety profile and a possible mechanism of vitamin D supplementation in inducing bactericidal pleiotropic effects has been suggested. To improve vitamin D status, high-dose vitamin D is required in the critically ill, as they display a blunted response to supplementation. Recent evidence suggests that treatment of vitamin-D deficient critically ill patients may improve outcomes and mortality, possibly through enhancing innate immunity and the inhibition of proinflammatory cytokines. Further clinical trials to explore the effects of vitamin D supplementation on the up-regulation process of proinflammatory cytokines are needed. 