Trauma induces a profound immunological dysfunction. This is characterised by an early state of hyperinflammation, followed by a phase of immunosuppression with increased susceptibility to infection and multiple organ failure. Therapeutic strategies directed at restoring immune homeostasis after traumatic injuries have largely failed in translation from "bench to bedside". The present review illustrates the role of biological modifiers of the posttraumatic immune response by portraying different modalities of therapeutic immune modulation. The emphasis is placed on anti-inflammatory (steroids) and immune-stimulatory (interferon) pharmacological strategies and modified resuscitative strategies, as well as more unconventional immunomodulatory approaches, such as immunonutrition.