Severely injured trauma victims are at high risk of development of the multiple organ dysfunction syndrome (MODS) or death. To maximize chances for survival, treatment priorities must focus on resuscitation from shock (defined as inadequate tissue oxygenation to meet tissue O2 requirements), including appropriate fluid resuscitation and rapid hemostasis. Inadequate tissue oxygenation leads to anaerobic metabolism and resultant tissue acidosis. The depth and duration of shock leads to a cumulative oxygen debt.1 Resuscitation is complete when the oxygen debt has been repaid, tissue acidosis eliminated, and normal aerobic metabolism restored in all tissue beds. Many patients may appear to be adequately resuscitated based on normalization of vital signs, but have occult hypoperfusion and ongoing tissue acidosis (compensated shock), which may lead to organ dysfunction and death. Use of the endpoints discussed in this guideline may allow early detection and reversal of this state, with the potential to decrease morbidity and mortality from trauma. Without doubt, resuscitation from hemorrhagic shock is impossible without hemostasis. Fluid resuscitation strategies before obtaining hemostasis in patients with uncontrolled hemorrhage, usually victims of penetrating trauma, remain controversial. Withholding fluid resuscitation may lead to death from exsanguination, whereas aggressive fluid resuscitation may disrupt the clot and lead to more bleeding. “Limited,” “hypotensive,” and/or “delayed” fluid resuscitation may be beneficial, but clinical trials have yielded conflicting results.2,3 This clinical practice guideline will focus on resuscitation after achieving hemostasis and will not address the issue of uncontrolled hemorrhage further.