Red blood cells are commonly administered to critically ill patients, yet the desired benefit of improving oxygen delivery and overall outcome may not be achieved in many scenarios. In addition, blood products are of limited supply and there are clear risks associated with blood transfusion. Despite this, studies show that almost half of all ICU patients receiving blood transfusions do so in the setting of stable anemia, suggesting that many critically ill patients in the ICU may receive unnecessary transfusions. Critical illnesses can lead to increased rates of anemia, even without active blood loss. The benefits of transfusion in these situations are unclear. Clear indications for blood transfusions, including uncontrolled hemorrhage, symptomatic anemia, and possibly acute coronary syndrome, are met in the minority of patients receiving red blood cell transfusions. This review discusses current evidence regarding the use of red blood cell transfusions in the ICU. Two major categories are examined, transfusion in patients noted to be anemic, but not clearly actively bleeding or symptomatic, and patients with aggressive bleeding who are critically ill or require massive transfusions.