For centuries, man has been trying to figure out how to revive sick and traumatized individuals using fluids of various types, even from animals. In the 17th century, it was determined that blood was the best fluid to use and, in the early 1900s, after the discovery of the ABO blood groups, human blood was found to provide significant benefit for patients with shock and/or anemia. In the 1950s and 1960s, various ways to obtain, process, and store human blood were developed. It soon became apparent that storage of human blood for transfusion was problematic because red cells, as they aged in vitro, underwent a multitude of physicochemical changes that greatly affected their shelf life, the so-called storage lesion. More recently, the question has arisen as to the potential detrimental effects of the storage lesion and suggestions that older blood may induce increased morbidity and even mortality despite its acceptable in vivo survival. To address this issue of the efficacy and safety of transfusion of aged stored blood, a number of controlled clinical trials have been instituted to determine if older blood is significantly detrimental compared with fresher blood in transfusion recipients.