A massive transfusion involves the administration of 10 units or more of whole blood or packed red blood cells (PRBCs) within 24 hours. An ultra-massive transfusion is defined as using more than 20 units of PRBCs within a 24- to 48-hour period. The primary objective of a massive transfusion is to prevent fatal outcomes resulting from critical hypoperfusion-related complications while striving to attain hemostasis. Furthermore, this topic explores the significance of major transfusion protocols (MTPs) and the indications, contraindications, and potential complications of this life-saving intervention. Patients across medical specialties may require massive transfusions. Although cardiac and vascular surgeries are the most common scenarios that necessitate massive transfusions, other frequent causes include gastrointestinal and obstetrical hemorrhages, liver transplants, and trauma. An estimated 3% to 5% of civilian trauma patients and 10% of military trauma patients typically undergo a massive transfusion. Although massive transfusions are relatively rare, patients in need of such transfusions often experience high mortality rates. As massive transfusions are unpredictable and require a substantial quantity of blood products over an extended duration, pre-planning among the emergency department, trauma service, surgical team, blood bank, and delivery personnel is essential. The Assessment of Blood Consumption (ABC) score is a tool for predicting the necessity of massive transfusions. Monitoring volume status, tissue oxygenation, bleeding management, coagulation abnormalities, and acid-base balance is imperative throughout a massive transfusion. The development and implementation of MTPs can effectively lower mortality rates and reduce the consumption of blood products.