Immunological complications frequently occur during the clinical course in patients with multiple injuries. The increased release of pro-inflammatory mediators during the immunological response to trauma may lead to the systemic inflammatory response syndrome (SIRS) and furthermore, to multisystem organ failure (MOF), which is associated with a mortality of up to 80%. The development of multiple organ failure following major trauma is associated with remote organ failure, the dysfunction of organs which were not initially affected by the trauma. This manuscript reviews recent data in experimental trauma research and offers a more detailed evaluation of the immunological findings in trauma patients. In particular, the role of pro- and anti-inflammatory cytokines in the development or SIRS, MOF and ROF is discussed. Despite the enormous progress in clinical immunology and the available data on trauma-induced immune dysfunction, a large number of questions still remain to be answered before the immunological alterations following severe trauma can be beneficially influenced by immunomodulatory therapeutic efforts.