Drotrecogin alfa (activated) is a human recombinant protein that is intravenously administered in a continuous, weight-based dose for patients with severe sepsis. In patients with severe sepsis, thrombin has been implicated in the interrelationship between the coagulation and inflammation pathways. Thrombin is responsible for conversion of fibrinogen to fibrin (thrombus formation). Thrombin also activates endothelial cells, white blood cells and platelets. Regulation of both the coagulation and inflammation pathways is in part through the interaction of thrombin and activated protein C. Activated protein C has particular attributes that may inhibit microvascular thrombi, promote fibrinolysis and directly dampen the proinflammatory aspect of infection. In patients with severe sepsis, many investigators have demonstrated an active coagulopathic state, with low protein C levels. A phase III clinical trial has demonstrated reduced mortality in severe sepsis patients receiving activated protein C.