One of the greatest challenges for critical care nurses today is managing the patient in multiple organ failure. As recently as 7 years ago, multiple organ failure was just being identified as a syndrome. Once identified, immediate prophylactic multisystem support was emphasized. Since then, there has been some measure of success in decreasing mortality, but further avenues must continue to be explored. Current research indicates that the unexplained, uncontrolled release of inflammatory mediators is a common occurrence in multiple organ failure. Because so much is yet unknown about the devastating effects of these mediators, it is even more imperative to monitor all body systems as early as possible, before irreversible damage occurs. One area that is often overlooked during multiple organ failure is the endocrine system. Normally volatile during any stressful period, the endocrine response may provide significant clues during the progression of multiple organ failure. Monitoring the endocrine response can help to control this progression. This article will heighten the critical care nurse's awareness of subtle changes in patient condition that are the result of endocrine dysfunction. Recognizing endocrine dysfunction will then help differentiate between reversible symptoms and those harmful effects of chemical mediators that are currently unbeatable. This enhanced understanding of the endocrine response will promote the ability to assess and comprehensively care for patients in multiple organ failure.