Recent evolution in the thinking of sepsis syndrome has provided a framework on which new clinical and basic research can be built. The separation of the inciting event and the cascade of subsequent physiologic changes has profound effects on how sepsis is thought of and ultimately how it will be treated. Early identification and treatment of infections and identifying patients at risk, to prevent SIRS, is the current role of Eps. Resuscitation of severe sepsis is more complex than other forms of shock and may require extensive resources if rapid admission or transfer to an intensive care unit is not available. As in many instances, the EP must be knowledgeable and skilled in the early identification and initial management of these patients until the definitive care can be provided. Modulation of the inflammatory response appears to be a prime prospect, but its practicality remains to be proved. Research and future roles of EPs include defining the population of ED patients at risk for SIRS and use of mediators of the inflammatory response. Emergency medicine is positioned in a critical point in the care of these patients.