A systemic inflammation with the release of multiple cytokines plays an important role in the pathophysiology of sepsis. During the last years, several anti-inflammatory substances have been investigated with respect to their effects on mortality in patients with sepsis. However, only the antibody fragment of the TNFalpha binding antibody afelimomab and the recombinant human activated protein C (drotrecogin alpha [activated]) were capable of improving the outcome in controlled studies with large sample sizes. The possible administration of these substances should be restricted to patients who meet the inclusion criteria of these studies. In particular, the tight time window, which usually ends 24 h after the onset of sepsis, should be taken into consideration before starting an anti-inflammatory medication. In addition to the anti-inflammatory treatment, the control of the infectious focus and an aggressive hemodynamic stabilization must not be neglected. Ibuprofen, interleukin-1 receptor antagonists and soluble TNFalpha-receptors as well as high dosages of corticosteroids and antithrombin III do not have a place in the anti-inflammatory treatment of sepsis.