Through a literature review, the epidemiology and pathophysiology, including alterations in inflammation, coagulation, and impaired fibrinolysis that occur in the course of severe sepsis, is presented. Treatment guidelines that are evidence-based and endorsed by 11 professional societies representing multispecialty groups are described. Severe sepsis is common; 750,000 cases are estimated to occur annually in the United States. The mortality rate for severe sepsis still ranges from 30 to 50%, and is as high as 80 to 90% for septic shock and multiple organ dysfunction. Severe sepsis exists along a continuum initiated by a localized infection that triggers a systemic response. A cascade of inflammation and activation of the coagulation system associated with impaired fibrinolysis leads to alterations in microvascular circulation associated with organ dysfunction, severe sepsis, multiple organ dysfunction syndrome, and death. In an attempt to improve care and reduce mortality, the Surviving Sepsis Campaign and The Institute for Healthcare Improvement (IHI) have created two sepsis treatment bundles.