TICS is a complex disease that is clearly multifactorial in the traumatically injured patient (Fig. 2). Although systemic inflammation that occurs directly as a result of injury plays the most prominent role, the local tissue and organ injury effects of trauma not only cause local capillary leak and edema but also further amplify the SIRS response. High volume fluid administration and hypoproteinemic states further exacerbate the problem. All of this leads to organ dysfunction and failure, which is the third leading cause of death following injury. Strategies to treat TICS and attenuate its effects once it occurs by targeting inflammatory pathways have been wholly unsuccessful. The mainstay of therapy for TICS is prevention and minimization of its lethal effects. Newer resuscitation strategies such as hemostatic resuscitation and early goal-directed therapies are currently the best available strategies to combat TICS. Whether these result in better outcomes remains to be seen and the authors anxiously await the results of well-designed prospective trials.