During the past 3 years new insights have been gained into the fundamental elements that underlie the pathogenesis of sepsis, and after years of frustrating failures, progress in the basic understanding of sepsis has translated into successful new therapies. These new treatment strategies have significantly improved the outcome of patients experiencing the puzzling syndrome of severe sepsis. More effective supportive therapies with early, goal-oriented therapy including volume resuscitation, catecholamine therapy and transfusion improve the chances for survival in septic shock. Novel endocrine management with hydrocortisone replacement therapy for relative adrenal insufficiency in septic shock patients and strict blood glucose control provide a survival advantage in critically ill patients. Administering appropriate antimicrobial therapy, nutritional support and ventilation protocols with low tidal volumes have now been shown to benefit septic patients. Finally, human recombinant activated protein C (drotrecogin alfa), which ameliorates sepsis-induced disseminated intravascular coagulation and exerts several other favourable effects on endothelial cells, has been shown to reduce mortality in patients with severe sepsis. On the basis of newly discovered pathophysiological mechanisms of sepsis, several other adjuvant therapies for sepsis are in various stages of preclinical and clinical development. Individualised and optimal supportive care with efforts to reverse the precipitating cause of sepsis remains the mainstay of therapy for severe sepsis. How these new and often expensive regimens will fit into the standard treatment approach to sepsis remains to be defined by future clinical investigations.