In the past, anemia in the perioperative period has been treated by red blood cell (RBC) transfusions relatively uncritically. RBC transfusions were believed to increase oxygen delivery by increasing hemoglobin concentration. Arbitrary transfusion triggers such as the “10/30 rule” (i.e., RBC transfusion indicated below a hemoglobin concentration of 10 g/dL or a hematocrit of 30%) were applied. However, there is now increasing evidence that RBC transfusions are associated with adverse outcomes and should be avoided whenever possible. Restraining from RBC transfusions and maintaining normovolemia in patients suffering from surgical blood loss results in acute anemia. Therefore, knowing the compensatory mechanisms during acute anemia is crucial. This review focuses on acute anemia tolerance, its limits, and physiologic transfusion triggers in the perioperative period.