Anemia is associated with perioperative mortality and morbidity. Since the presence of anemia and blood transfusion often go hand in hand, it can be difficult to separate the effects of anemia from the effects of perioperative transfusion. The role for blood transfusion in mitigating the mortality and morbidity associated with anemia is unclear. A restrictive transfusion strategy has been advocated for hemodynamically stable patients, as blood transfusion exposes the patient to both infectious and non-infectious complications. Further research is warranted in patients with the acute coronary syndrome, as there is insufficient evidence to make recommendations for this patient population. Additional multi-center randomized controlled trials need to be conducted in perioperative and critically ill patients with large enough sample sizes to examine differences in mortality and major complications between liberal and restrictive transfusion strategies. Further trials need to incorporate current practices in improved blood storage and leukoreduction techniques.