Shock resuscitation is an obligatory intervention for severely injured patients who present in shock. During the past 15 years, with widespread acceptance of “damage control” surgery and early triage to the intensive care unit (ICU) to optimize resuscitation, the lives of many major trauma victims have been saved, and much has been learned about shock resuscitation. Due largely to the work of Shoemakeret al., a resuscitation strategy based on a standardized process using O2delivery index (DO2I) as an endpoint and physiologic performance goal for interventions has been developed, studied, and refined for resuscitation of shock caused by major trauma. DO2I ≥600 mL O2/min-m2is the only resuscitation endpoint variable that has been tested in prospective randomized trials (PRTs) of trauma patient outcome. These PRTs are limited, and their results are not conclusive. Results from other investigators, including our group, using similar process and endpoints, are indicating similar performance and outcomes. We believe that DO2I is a useful endpoint because it integrates three important variables,ie,hemoglobin concentration [Hb], arterial hemoglobin O2saturation, and cardiac output. We have found DO2I ≥500 mL O2/min-m2to be an endpoint with more general applicability, but we believe that the standardized process is more important than the specific endpoint. To standardize our process, we have developed a computerized decision support tool for shock resuscitation. This technology has provided novel data collection and has permitted refinement of the bedside process. Our data analysis indicates that the next challenge will be to develop a similar pre ICU resuscitation process that will use less invasive monitors and different endpoints. Identification of the high-risk resuscitation nonresponders early in the resuscitation process will be needed to redirect their clinical trajectories. As an endpoint for interventions for goal-directed resuscitation in the critically injured trauma patient, systemic O2delivery is the current state of the art and the basis for near future development of clinical processes for resuscitation of shock due to major trauma.