Although multiple studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by applying diagnosis and therapy at the most proximal stage of hospital presentation (before intensive care unit arrival), this approach to the sepsis patient has been lacking. In response to this, a trial comparing early goal-directed therapy (EGDT) versus standard care was performed using internally and externally validated criteria for early identification of high risk patients, established definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression and increased metabolic demands. That trial of EGDT resulted in significant reductions in morbidity, mortality, vasopressor use, and health care resource consumption. The end-points used in the protocol and the outcome results were subsequently externally validated, revealing similar or better mortality benefit. This commentary examines the rational and validation for the use of early markers of illness severity. Current evidence support the endpoints in the EGDT protocol, external validity in regards to outcome benefit and the universal need to improve the quality of care for early sepsis.A recent retrospective, observational study by Ho and coworkers [1] measured the incidence and outcome of septic patients presenting at an Australian emergency department (ED) with criteria for early goal-directed therapy (EGDT) and found significantly fewer EGDT candidates than previous studies [2]. A number of initiatives aiming to reduce worldwide mortality associated with sepsis, such as the Surviving Sepsis Campaign, have previously noted the importance of the tenets of early hemodynamic optimization to try and overcome this devastating disease. In patients with severe sepsis or septic shock, clinicians must be aware that a considerable proportion of those with significant lactic acidosis can have near normal serum bicarbonate or normal calculated anion gap values, which may lead to underestimated disease severity [3][4][5]. In the EGDT study [2], of the patients enrolled with a lactate level greater than 4 mmol/l, more than 30% had a bicarbonate level greater than 22 and an anion gap of less than or equal to 15 mEq/l. Other studies have shown that even if an anion gap is present, the mortality rate is significantly higher for lactic acidosis (56%) than for strong ion gap acidosis (39%) and hyperchloremic acidosis (29%) [6]. Despite mentioning lactate as a criterion in the study, Ho and coworkers did not report data regarding the levels or number of measurements found. Thus, it is possible that they underestimated the prevalence of high-risk patients in need of early hemodynamic optimization. This may explain why they strikingly found only 50 patients over 3.5 years (14.2 per year) meeting criteria for severe sepsis and septic shock in a large teaching hospital emergency department (ED) that sees 40,000 patients each year with a 30% admission rate.The lactate level ...