Wilson et al3 wrote a series of expert opinions beginning in 1976 that comprise the tenets of early sepsis management. These recommendations included early identification of high-risk patients, appropriate cultures, source control, and appropriate antibiotic administration. This is followed by early hemodynamic optimization of preload (central venous pressure [CVP] or surrogate); afterload (mean arterial pressure); arterial oxygen content (hemoglobin); contractility (avoiding tachycardia); and balancing systemic oxygen delivery and consumption, using central venous oxygen saturation (Scvo2) as an end point. More than a decade ago, these sepsis interventions (also recommended by the American College of Critical Care Medicine and the Society of Critical Care Medicine4) were applied at the most proximal stage of presentation, which mirrors the approach to trauma, stroke, and acute myocardial infarction. This approach, called early goal-directed therapy (EGDT), was tested against standard care in a randomized controlled trial, and an outcome benefit of > 16% was realized (Fig 1). Ironically, the institutional review board, after noting a prestudy mortality of > 50%, requested that the standard care arm be upgraded from actual care because it would be an unethical comparison.