Severe sepsis is a common disease process affecting some 2-11% of hospital admissions in the US. Severe sepsis and septic shock are associated with considerable morbidity and mortality, and account for a large part of intensive care unit costs. Until recently, the management of septic shock relied on the treatment of underlying infection with antimicrobial agents and surgical removal of any infectious source, and individual support of failing organs. However, in the last few years we have seen huge strides being made in our understanding of the pathophysiology of the sepsis response, and in our ability to manipulate that response. In the last couple of years these advances have come to fruition with the development of a drug, drotrecogin alfa, which specifically reduces mortality from this all too often fatal disease. While intensive early resuscitation remains the cornerstone of management, new approaches are beginning to form part of sepsis management protocols and will lead to improved outcomes for patients with this disease process.