The Surviving Sepsis Campaign (SSC) was launched in 2002 as a collaborative initiative of the European Society of Intensive Care Medicine (ESICM), the International Sepsis Forum (ISF), and the Society of Critical Care Medicine (SCCM). Its objective was, through the development and promulgation of evidence-based guidelines that facilitated the application of knowledge derived from clinical trials to bedside practice, to effect a 25% reduction in the relative risk of death from severe sepsis and septic shock. The evolution and content of the SSC is summarized and the scientific basis of the conclusions is reviewed from the literature. The SSC developed evidence-based management guidelines and undertook a broad educational program to implement them by integrating their recommendations into resuscitation and management bundles. The process engaged practitioners in North America, Europe, and South America and was supported by professional societies around the world. It also engendered controversy based on accusations of undue industry influence and some dissatisfaction among individuals who were antagonistic toward protocolization of care. By its conclusion, more than 22,000 patients with sepsis had been entered in the SSC database, and analysis of the results showed that participation in the SSC was associated with a 5.4% absolute survival benefit. The SSC has impacted the care of septic patients and catalyzed changes that are likely to persist and evolve.