Systemic inflammatory response syndrome (SIRS) and its lethal sequela multiple organ dysfunction syndrome (MODS) are common complications in critical illness, such as severe trauma, shock, infection and major operations. During the past three decades, the evolution in our understanding of SIRS and/or MODS could be divided into three stages. Particularly in recent years, advances in molecular and cellular biology have provided new insights in the pathogenesis of this complex condition. The earlier emphasis on the pro inflammatory mediators involved in propagation of inflammatory response, has gradually been replaced by a realization that SIRS/MODS are the result of an imbalance of pro and anti inflammatory mediators to create the final status of excessive inflammation or immunoparalysis’. Though prognosis remains poor, the knowledge that now exists about SIRS/MODS gives great hope for the future. Progress has been made in new treatment modalities and re evaluation of current available measures. Nevertheless, improved techniques to monitor immunological or other markers of inflammatory and host defense responses will be important in assessing the effects of future therapies on central mechanisms contributing to SIRS/MODS.