Sepsis is among the most common causes of death in intensive care unit patients in both North America and Europe. In the US it accounts for upwards of 250,000 deaths each year [1]. Despite this, the importance of sepsis as a public health problem is under-appreciated. This in-part stems from changing definitions. The dictionary definition invokes the presence of dividing micro-organisms in the blood. However, this has proven to be too narrow. The first systematic approach to the classification of sepsis, the 1992 Society of Critical Care Medicine (SCCM)/American College of Chest Physicians (ACCP) Consensus Conference, clarified some of the diagnostic criteria and also first introduced the concept of the systemic inflammatory response syndrome (SIRS)[2]. This entity was defined on the basis of temperature, heart rate, respiratory rate and white blood cell counts. While useful in defining entry criteria for clinical studies, this approach has proven to be too general and nonspecific. Therefore, the 2001 revision jointly sponsored by the SCCM and the European Society of Intensive Care Medicine (ESICM) is based on the presence of general variables, inflammatory variables, hemodynamics, organ dysfunction and tissue perfusion. Significantly, the concept that sepsis of necessity involves infection has been eliminated. This is important for two reasons. First, no organism is ever identified in upwards of 50% of patients who die with a diagnosis of sepsis. Second, systemic infection and similar inflammatory states give rise to a more recently appreciated entity, the multiple organ dysfunction syndrome (MODS)[3]. This clinically-defined common final pathway may develop in patients with severe infection but also following severe trauma, aortic aneurysm rupture, amniotic fluid embolism and a host of other conditions. The development of MODS suggests that the pathogenesis of sepsis cannot be due solely to invading organisms but rather must reflect the host response to some severe insult. The search for a primary defect and the mechanism by which it impairs function in a broad array of cells and organs has been the focus of intense investigation for several decades.