Sepsis is a clinical syndrome defined by a systemic response to infection. With progression to sepsis-associated organ failure (ie, severe sepsis) or hypotension (ie, septic shock) mortality increases. Sepsis is a cause of considerable mortality, morbidity, cost, and health care utilization. Abnormalities in the inflammation, immune, coagulation, oxygen delivery, and utilization pathways play a role in organ dysfunction and death. Early identification of septic patients allows for evidence-based interventions, such as prompt antibiotics, goal-directed resuscitation, and activated protein C. Appropriate care for sepsis may be more easily delivered by dividing this clinical entity into various stages and with changes in structures of delivery that extend across traditional boundaries. Better description of the molecular basis of the disease process also will allow for more targeted therapies.