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With an increasing incidence of sepsis, increasing use of the emergency department by populations at risk, and an increase in time spent in the emergency department awaiting hospital admission, emergency medicine practitioners are offered a valuable opportunity to make a significant difference in the fight against sepsis. By administering appropriate antibiotics in a timely fashion, removing possible sources of infection, practicing early goal-directed hemodynamic optimization, using lung-protective ventilation strategies, and judiciously using corticosteroids and intensive insulin therapy, the goal of reducing mortality from sepsis can be achieved.