Abstract Background Localized inflammation is a physiological protective response which is generally tightly controlled by the body at the site of injury. Loss of this local control or an overly activated response results in an exaggerated systemic response which is clinically identified as systemic inflammatory response syndrome (SIRS). Compensatory mechanisms are initiated in concert with SIRS and outcome (resolution, multiple organ dysfunction syndrome or death) is dependent on the balance of SIRS and such compensatory mechanisms. No directed therapies have been successful to date in influencing outcome. Method This review examines the current spectrum and pathophysiology of SIRS. Results and conclusion Further clinical and basic scientific research is required to develop the global picture of SIRS, its associated family of syndromes and their natural histories.