This article documents that all immunomodulation strategies for patients sustaining traumatic injury are still under intense investigation. Although we can speculate that combination strategies may be more beneficial than single-agent immunomodulation approaches, comprehensive clinical studies are required to determine efficacious immune therapy for trauma patients. The only strategy available to clinicians caring for trauma patients is immunonutrition, and this should be strongly considered as a rational approach to improve immune function and reduce septic complications in critically ill or injured patients.