Anemia is common in the ICU, increasing morbidity and mortality. Its etiology is multifactorial but anemia of inflammation is the most common cause, followed closely by iron deficiency. The two conditions often coexist and it can be difficult to diagnose iron deficiency in the context of anemia of inflammation. Blood transfusions and use of erythropoietin agonists are two modalities used to correct anemia in critically ill patients. Randomized controlled trials have not supported the use of either therapy except in well defined clinical situations. Better understanding of the pathophysiology of anemia of inflammation may lead to development of novel therapies.