With the advent of blood banks and subsequent advances in collection and preservation of blood, the transfusion of blood allowed the performance of blood-losing surgery and the support of rigorous cancer treatments, as well as the support of patients who have hematologic illnesses. As the life-saving functions of transfusion were realized, so were the associated hazards inherent in this most widely performed type of tissue transplantation. This article reviews the quality initiatives that have been used to make blood transfusion safer and offers suggestions for further quality improvements.