An impaired function of the protein C pathway plays a central role in the pathogenesis of sepsis. Administration of human recombinant activated protein C (Xigris) may restore the dysfunctional anticoagulant mechanism and prevent amplification and propagation of thrombin generation and formation of microvascular thrombosis but may simultaneously modulate the systemic pro-inflammatory response. Experimental studies indicated that the administration of activated protein C could block the derangement of coagulation, inhibit inflammatory effects and preserve organ function. Randomised controlled clinical studies in patients with severe sepsis confirmed these beneficial effects and demonstrated that administration of recombinant human activated protein C resulted in a reduction of mortality in patients with severe sepsis.