Nutrients have traditionally been viewed as a means to provide basic calories to sustain homeostasis. However, critically ill, surgical, and trauma patients are in a constant dynamic state between systemic inflammatory response (SIRS) and compensatory anti-inflammatory response (CARS). Results from ongoing research strongly support the use of specific nutrients to modulate the immune and/or metabolic response. These agents can now be considered therapeutic tools in the management of complex hypermetabolic diseases. The principle of using nutrients as a therapeutic strategy rather than just as "nutritional support" requires a shift in the current dogma. The most common nutrients found in currently available enteral immune-modulating formulas are omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid), antioxidants, nucleotides, glutamine, and arginine. Multiple individual reports and at least five meta-analyses using combinations of immune-modulating nutrients have reported almost uniform beneficial results. However, certain conflicting hypotheses continue to revolve around the use of arginine in septic patients.