Massive transfusion protocol (MTP) implementation has been shown to reduce treatment variability, patient mortality, length of hospital stays, and blood utilization. The primary objective of an MTP is to avoid coagulopathy development in bleeding patients through the administration of blood products in a standardized, empirically driven manner. Although MTP activation is currently based on many different criteria, a decision to trigger an MTP requires clinical judgment that is best guided through standardized decision aides and the patient’s overall clinical profile, and not isolated physiologic or hematologic variables. Current best evidence for intraoperative massive transfusion supports application of trauma-derived, balanced ratios of 1:1 for plasma/RBC (with less clear guidance for platelet ratios). Unlike MTP dosing in the adult patient population, pediatric MTPs apply weight-based product dosing for smaller patients. Once vital signs and bleeding have stabilized, transition from an MTP to goal directed management with coagulation testing is necessary, and the MTP should be deactivated to avoid blood product overuse or wastage. MTP deactivation is an active communication process. An increasing number of pediatric studies demonstrate relative efficacy and safety of fibrinolytics when administered in the perioperative setting, and they are now a standard element of the MTP.