Sepsis, severe sepsis, and septic shock impose a growing economic burden on health care systems globally. This article first describes the epidemiology of sepsis within the United States and internationally. It then reviews costs associated with sepsis and its management in the United States and internationally, including general cost sources in intensive care, direct costs of sepsis, and indirect costs of the burden of illness imposed by sepsis. Finally, it examines the cost-effectiveness of sepsis interventions, focusing on formal cost-effectiveness analyses of nosocomial sepsis prevention strategies, drotrecogin alfa (activated),and integrated sepsis protocols.