The treatment of sepsis consists of focus control as well as supportive and adjuvant therapy. Especially the last option has been investigated during the last years. Different approaches showed promising results in animal experiments and phase-I trials but did not prove to be successful in large multicenter studies. The application of TNF-receptors or interleukin-1 receptor antagonists did not lead to an improvement of outcome in patients with sepsis. Most studies with TNF-antibodies also presented negative results. However, a recent large study with a monoclonal antibody against TNFalpha demonstrated a significant survival benefit. The recently published PROWESS study is the first investigation demonstrating the decrease of mortality in patients with sepsis after administration of protein C. Additionally, current data support the low-dose hydrocortisone therapy in patients with vasopressor dependent septic shock.