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Useful resuscitation endpoints must serve both to diagnose the need for and to ensure the ongoing adequacy of resuscitation. To this end, traditional measures of organ perfusion are now widely appreciated to be grossly inadequate. Useful endpoints or milestones range from the global, to the regional, to the cellular specific. Understanding the basic principles of perfusion-related dysoxia in trauma and hemorrhage and its potential rapid transition to involve inflammatory and immune responses on cellular oxygen utilization will aid the clinician in choosing and appropriately interpreting endpoint monitoring data. There also appears to be an optimal window of opportunity for monitoring to help mitigate the development of more complicated inflammatory states. This article reviews the underlying need for endpoint selection (both global and regional, biochemical and functional) and monitoring during resuscitation of the polytrauma patient. At this juncture it appears that early use of a blend of global markers such as lactate and base deficit coupled with an available sensitive regional monitor such as gastric tonom-etry may offer the best combination of current technology to guard against early perfusion-related dysoxia. Future techniques involving optical spectroscopy offer the exciting potential to assess oxygenation at the cellular level. This may aid in ultra-early detection and resolution of perfusion-related dysoxia in addition to recognizing its transition to more complex inflammatory-mediated circulatory and metabolic failure.