Despite the frequent use of red cell transfusions, only one large randomized trial has examined red cell administration perioperative and in the critical care setting. However, the TRICC Trial does not provide sufficient evidence to determine optimal transfusion practice in postoperative care, in critically ill children, or in patients with a myocardial infarction or acute coronary syndromes. In addition, most transfusion practice guidelines published before the completion of the TRICC Trial are now dated and need to have expert opinion informed by solid evidence in diverse clinical settings. In the next several years,several randomized trials will provide additional evidence in support of bedside decision-making. For example, two transfusion studies will be evaluating transfusion triggers, including one in premature infants and the other in critically ill children. At this juncture, high-quality clinical evidence is not yet available for many decisions related to red cell transfusions. We anticipate that risks and benefits of red cells and alternatives will be elucidated in the coming years.