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SIRS (the Systemic Inflammatory Response Syndrome) and MODS (the Multiple Organ Dysfunction Syndrome) are not diseases or syndromes, but concepts. Common to both is the notion that the morbidity of critical illness arises indirectly, from the response of the host to an acute, life-threatening challenge to systemic homeostasis. The biology of that response is complex and variable, yet implicit in our evolving understanding of systemic inflammation is the possibility that shared biologic mechanisms may permit the development of effective therapy for a wide variety of disorders that appear superficially heterogeneous. The challenge lies in characterizing common pathologic processes or diseases. The four criteria that define SIRS are non-specific measures of physiologic severity, rather than distinctive manifestations of a disease process. Perhaps the use of the systemic correlates of the cardinal manifestations of inflammation developed by Galen and Celsus would provide a more satisfactory clinical characterization of the clinical disorder. However, the complexity of the biologic processes involved suggest that a clinical syndrome of systemic inflammation is of no more use to the clinician than a clinical syndrome of cancer. As the functio laesa of systemic inflammation, organ dysfunction is more appropriately viewed as an undesireable outcome of systemic inflammation, a complication to be prevented, rather than a disease to be treated. As concepts, SIRS and MODS provide a useful intellectual framework for investigation, but the clinician must treat diseases, no acronyms. The challenge will be to characterize these disease.