Sepsis and the systemic inflammatory response syndrome are common and represent a major factor in morbidity and mortality in intensive care units and the critically ill. The pathogenesis of these syndromes is becoming increasingly understood and it is hoped that this will result in improved outcome. However, novel treatments have so far failed to live up to the expectations following extensive and promising in vitro and in vivo animal studies. The aim of this review is to detail the currently used definitions of systemic inflammatory response syndrome, sepsis and septic shock and to present an overview of our current understanding of the pathophysiology which underline these conditions.