The metabolic derangements of the injured or stressed patient are governed by multiple factors that partially include the severity of insult, preexisting illnesses, available energy reserves, and appropriateness of intervention. The normal response to injury is further characterized by the release of proinflammatory and antiinflammatory mediators that exert potent effects on cellular and organ function. Although brief periods of starvation and catabolism are tolerable in otherwise healthy individuals, protracted nutritional deprivation can manifest as immunocompromise, irreversible organ injury, and late mortality. Moreover, patients with severe injuries or preexisting illnesses who exhibit exaggerated inflammatory responses may be further predisposed to such deleterious consequences following the insult. The optimal supply of appropriate nutrients and substrates in such circumstances has often been championed as a necessary means of restoring proper cellular metabolism, wound healing, immune competence, and proper organ function. However, much debate surrounds the present efficacy of nutritional therapy in modulating the immune response associated with injury and stress. This article seeks to assess the merits of nutritional therapeutics in the injured patient through available biological and clinical evidence.