The anemia of critical illness is a distinct clinical entity with characteristics similar to that of chronic disease anemia. Several solutions to the processes of anemia, such as blunted erythropoietin production and erythropoietin response and abnormalities in iron metabolism have been developed. The transfusion of RBCs provides immediate correction of low hemoglobin levels, which may be of value in patients with life-threatening anemia. Avoidance of RBC and blood component transfusion, however, is becoming increasingly important as data of adverse clinical outcomes in critically ill patients become clearer. Although the optimal hemoglobin in critically ill patients is not determined, this organ system has a generous reserve. Short-term compensated anemia is tolerated well, while exogenous erythropoietin allows patients to achieve higher hemoglobin concentrations without exposure to transfused blood/blood components. A recent randomized trial enrolled over 1300 critically ill patients to receive either 40,000 units of exogenous erythropoietin or placebo. These authors found that patients randomized to erythropoietin received significantly less allogeneic RBC transfusions and had significantly greater increases in hemoglobin. Although no differences were found between groups in gross clinical outcomes (ie, death, renal failure, myocardial infarction), this study did not have the power to identify small differences in outcomes. This and other studies of exogenous erythropoietin therapy in critically ill patients clearly demonstrate that the bone marrow in many of these patients will respond to the administration of erythropoietin despite their illness, suggesting a blunted production of erythropoietin rather than a blunted response to erythropoietin. Exogenous erythropoietin therefore represents a therapeutic option for treating anemia in critical illness. Acute events in medicine and surgery often lead to many patients becoming anemic. Solutions to this process of anemia should be focused on preventing such events. Anemia after surgery represents an area for prevention. Blood conservation strategies can be performed with adequate results. Monk et al randomized 79 patients undergoing radical prostatectomy to preoperative autologous donation (PAD), preoperative exogenous erythropoietin therapy plus ANH immediately following induction of general anesthesia, and ANH alone. This study concluded that all three techniques resulted in similar hemostasis outcomes (eg, bleeding and transfusion rates), but ANH alone was the least expensive, and ANH plus exogenous erythropoietin and ANH alone resulted in a higher ICU hematocrit compared with PAD. Regardless of these prophylactic strategies, patients still become anemic after surgery or during critical illness. This acute event anemia usually is treated with RBC transfusion; however, autologous blood recovery (cell salvage systems) has been shown to be effective in patients with acute bleeding-related anemia, and this may reduce patients' exposure to allogeneic blood in these patients. There are no universally accepted treatment guidelines for managing anemia, and practice differs between clinicians, hospitals, regions, and countries. Transfusion medicine is evolving and incorporating many new pharmacological agents into the armamentarium of anemia and bleeding therapy. Accumulating evidence suggests that anemia in critically ill patients is common and correlated with poor outcomes. The management of anemia can improve outcomes; however, the optimal management of anemia is not performed universally. New approaches, continued research, and an understanding of anemia may result in more consistent and improved outcomes for critically ill patients.