Sepsis is one of the most common conditions encountered in the intensive care unit and is the 10th leading cause of death overall in the United States. Both long-term survival and health-related quality of life are reduced in survivors of sepsis, yet there is little knowledge of the effect of sepsis-specific interventions on either long-term survival or health-related quality of life. The present article discusses the importance of studying health-related quality of life as it relates to sepsis management strategies, particularly in the context of pharmacologic therapy with recombinant human activated protein C.