Severe sepsis and septic shock are still the leading causes of death in the surgical ICU. The only curative therapies of sepsis are still surgery as well as antibiotic therapy to cure the focus. In addition a supportive therapy (analgesia and sedation, mechanical ventilation, titrated volume substitution and positive inotropes/vasopressor support, parenteral and enteral neutron, renal replacement therapies) should be started as early as possible. A new promising approach in sepsis therapy is the application of rhAPC. The PROWESS study revealed a significantly lower 28 day mortality in patients with severe sepsis who received drotrecogin alfa (activated) compared to patients not treated with drotrecogin alfa (activated). Guidelines for the use in severe sepsis and septic shock in surgical patients (risk of bleeding, costs) are strongly recommended.