Each year, more than 4 million patients receive a blood transfusion in the United States to control symptoms associated with anemia, coagulopathy, thrombocytopenia, or some combination thereof. In each of these cases, the physician and the patient must weigh the potential benefits of the transfusion along with the associated risks. To assess accurately the risk:benefit ratio and to discuss this with the patient, the physician must be familiar with the range of adverse transfusion outcomes and the current estimates of their frequency. Most important, during the past decade the risk profile of transfusion has changed significantly. Transfusion-transmitted disease, although still a rare outcome of transfusion, is no longer an overriding concern in transfusion safety considerations; however, risks such as hemolysis, transfusion-related lung injury, and anaphylaxis continue to represent significant concerns and are relatively more common than the transmission of infectious diseases after transfusion. Against this background, the development of a national hemovigilance system, designed to evaluate more accurately transfusion adverse outcomes in the United States, will require greater precision and reliability in the assessment of adverse transfusion outcomes by clinicians if the proposed benefits of this system are to be realized.