The immunological sequelae following multiple trauma constitute an ongoing challenge in critical care management. The overall immune response to multiple trauma is a multilevel complex interdependently involving neurohormonal, cellular and haemodynamic factors. Immunoparalysis is characterised by a reduced capacity to present antigens via downregulated HLA-DR and an unbalanced monocyte-T cell interaction. Trauma-induced death of functionally conducive immune cells in the early recovery phase is significant in the emergence of posttraumatic multiple organ dysfunction or failure. Novel findings may contribute to more appropriate immunomonitoring and improved treatment. We must consider the preservation and support of immune function as the ultimate therapeutic goal, which may override the current strategy of simply antagonising excessive pro- or anti-inflammatory immune responses of the severely injured person. This review focuses on the injury-induced conduct of key immune effector cells and associated effects promoting immunoparalysis after multiple trauma.