Coagulopathy and systemic inflammation are almost universal in patients with severe sepsis. Interaction between the two results in an intense inflammatory response and microthrombi formation in the vessels of multiple organs, resulting in organ dysfunction or severe sepsis. Recombinant human activated protein C, also known as drotrecogin alfa (activated), possesses anti-inflammatory, antithrombotic, and profibrinolytic properties. Treatment with drotrecogin alfa (activated) significantly reduces morbidity and mortality in patients with severe sepsis. An increased risk of bleeding during the infusion was the only side effect experienced. Recent data demonstrate that early administration of drotrecogin alfa (activated) is associated with lower mortality rates. Despite concern over its relatively high cost, analysis has demonstrated that recombinant human activated protein C is as cost-effective as other commonly used treatments in the intensive care unit.