Sepsis results from the host response to infection. While a localized and controlled inflammatory reaction helps to control infection, a dysregulated response may lead to multiple organ failure and determines the course and prognosis of the septic patient. Despite intensive care, mortality remains as high as 54% for severe sepsis and septic shock. As the mechanisms are becoming better defined, interventions aiming to interfere with the host response have been undertaken, largely with disappointing results. Thus, many evidence-based recommendations suggest waiving of resource-consuming interventions. Nevertheless, several seminal studies have indicated that early and systematic supportive therapy according to pathophysiological principles, most notably early goal-directed therapy, low-dose hydrocortisone and activated protein C, can disrupt dysfunctional cascades and can favourably influence the course of the disease. In parallel, efforts to better define nationwide epidemiology and treatment habits for severe sepsis by the German competence network "SepNet" indicate that therapy of severe sepsis is generally in poor compliance with guidelines, while the personal perception of physicians in charge would suggest high rates of adherence. Thus, strategies of change management, such as implementation of sepsis bundles are warranted to achieve a better standard of care toward the aim of the "surviving sepsis campaign", i.e. a reduction of mortality by 25% within the next 5 years.