The development of organ dysfunction (OD) is related to the intensity and balance between trauma-induced simultaneous, opposite inflammatory responses. Early proinflammation via innate immune system activation may cause early OD, whereas antiinflammation, via inhibition of the adaptive immune system and apoptosis, may induce immunoparalysis, impaired healing, infections, and late OD. Patients discharged with low-level OD may develop the persistent inflammation-immunosuppression catabolism syndrome. Although the incidence of multiple organ failure has decreased over time, it remains morbid, lethal, and resource intensive. However, single OD, especially acute lung injury, remains frequent. Treatment is limited, and prevention remains the mainstay strategy.