Hemorrhage remains a leading cause of morbidity and death in both civilian and military trauma. Restoration of effective end-organ perfusion by stopping hemorrhage and restoring intravascular volume in such a way as to minimize acidosis, hypothermia, and coagulopathy, almost always requires the use of blood and/or blood-component therapy. The best method to manage life-threatening hemorrhage is to avoid the circumstance that prompted it or to mitigate blood loss early in the injury cycle; otherwise, blood replacement must suffice. This article reviews current understanding of massive transfusion, along with its attendant unintended consequences, in the management of patients with profound hemorrhage.