While many studies have reported that providing parenteral nutrition (PN) can change nutritional outcomes, there are limited data that demonstrate that PN influences clinically-important end points in critically-ill patients. The purpose of the present paper is to systematically review and critically appraise the literature to examine the relationship between PN and morbidity and mortality in the critically-ill patient. Studies comparing enteral nutrition (EN) with PN and studies comparing PN with no PN were reviewed. The results suggest that EN is associated with reduced infectious complications in some critically-ill subgroups. PN, on the other hand, is associated with increased morbidity and mortality in critically-ill patients. When nutritional support is indicated, EN should be used preferentially over PN. Further studies are needed to define the optimal timing and composition of PN in patients not tolerating sufficient EN. Strategies to optimize EN delivery and minimize PN utilization in critically-ill patients are indicated.