In order to maximize the benefit of prompt antimicrobial therapy and avoid the risk associated with inappropriate use of antimicrobial agents, patients with suspected sepsis must be rapidly differentiated from patients with systemic inflammatory response syndrome (SIRS). In combination with standard microbiological testing, a number of biomarkers have been recently evaluated for this purpose, and the performance characteristics of the most promising of these are reviewed.T he title of this minireview is somewhat misleading, because sepsis is not a laboratory diagnosis and cannot be defined (at least not yet) using any number of discrete diagnostic assays in the absence of clinical criteria. A positive blood culture, for example, regardless of the organism's identity, is useful supplemental information but does not by itself indicate a septic state. In fact, the recovery of a potential pathogen from any site (1), including blood (2), occurs in less than 50% of all cases of sepsis, and contamination of blood cultures can cloud the interpretation. From the opposite direction, it is difficult to distinguish sepsis from systemic inflammatory response syndrome (SIRS) using clinical criteria alone (3).A few definitions might help clarify the ambiguity here (4, 5). Some of these definitions have been refined over the years, but the general gist remains the same. "SIRS" was first defined in 1991 (4) and refers to "the systemic inflammatory response to a variety of severe clinical insults" (infectious or otherwise). It usually constitutes two or more of the following criteria: (i) temperature of Ͼ38°C or Ͻ36°C; (ii) heart rate of Ͼ90 beats/min; (iii) respiratory rate of Ͼ20 breaths/min or partial CO 2 pressure (pCO 2 ) of Ͻ32 mm Hg; (iv) white blood cell (WBC) count of Ͼ12,000 (12K)/l or Ͻ4K/l; or (v) Ͼ10% immature forms (i.e., bands). "Sepsis" has been defined as "the presence (probable or documented) of infection together with systemic manifestations of infection" (5). Having positive cultures supporting an infectious process adds credibility to the diagnosis but is not mandatory. Therefore, a patient can be classified as septic with Ն2 SIRS criteria and a clinical suspicion of infection without microbiological documentation. Bear this in mind when reading the remainder of this minireview. Most septic patients have SIRS, but not all SIRS patients are septic (Fig. 1). Severe sepsis adds an element of organ dysfunction or tissue hypoperfusion that is new and not explained by other causes of organ dysfunction (4). Finally, "septic shock" is "sepsis-induced hypotension persisting despite adequate fluid resuscitation" (4). Definitions specific for adult and pediatric populations are available (4-6).Sepsis is a major cause of morbidity and mortality among critically ill patients, and the management of septic shock profits from administration of early and appropriate antimicrobial therapy (7). Given that sepsis is only a subset of SIRS and that administration of antimicrobial therapy is not beneficial and indeed could generate...