Recognition of the acute coagulopathy of trauma and the limits of reconstituting whole blood with conventional blood components has led to a radical change in the way trauma patients with severe injuries are resuscitated. Massive transfusion protocols (MTP) have evolved toward the administration of conventional blood components in fixed ratios. Administration of a 1:1:1 unit ratio of fresh frozen plasma to whole-blood–derived platelets to packed red blood cells is now the most common strategy and the stated goal of directors of >80% of the level I trauma centers in the United States. Various physiologic scoring systems exist to guide early activation of an MTP. After activation of an MTP, more goal-directed therapy follows as soon as laboratory results are available. Hemostatic resuscitation using defined blood component ratios modified by early laboratory results can lead to more efficient blood product usage and improved patient outcomes.