Sepsis is a complex clinical condition that is driven predominantly by deviations from the orderly stereotypic immunological response to infection. Much effort has been undertaken in the search for biomarkers that can assist in discriminating critically ill patients with sterile inflammation from those with sepsis. Such biomarkers may aid the clinician in therapeutic decision making upon admission of a patient. Interleukin-27 may be such a discriminative biomarker, as suggested in the previous issue of Critical Care by a study of critically ill children.