Morphologic and biochemical changes occur during red cell storage prior to product expiry, and these changes may hinder erythrocyte viability and function following transfusion. Despite a relatively large body of literature detailing the metabolic and structural deterioration that occurs during red cell storage, evidence for a significant detrimental clinical effect related to the transfusion of older blood is relatively less conclusive, limited primarily to observations in retrospective studies. Nonetheless, the implication that the transfusion of old, but not outdated blood may have negative clinical consequences demands attention. In this report, the current understanding of the biochemical and structural changes that occur during storage, known collectively as the storage lesion, is described, and the clinical evidence concerning the detrimental consequences associated with the transfusion of relatively older red cells is critically reviewed. Although the growing body of literature demonstrating the deleterious effects of relatively old blood is compelling, it is notable that all of these reports have been retrospective, and most of these studies have evaluated patients who received a mixture of red cell units of varying storage age. Until prospective studies have been completed and produce confirmative results, it would be premature to recommend any modification of current transfusion practice regarding storage age. In 1917, Frances Payton Rous and J.R. Turner identified that a citrate-glucose solution allowed for the preservation of a whole blood unit for up to five days, thus facilitating the formative practice of blood banking. Later, Loutit and Mollison of Great Britain developed the first anticoagulant of the modern era, known as acid-citrate-dextrose (ACD). ACD extended the shelf life of refrigerated blood to 21 days, and ACD remained in wide spread usage until the 1960s, when it was replaced by citrate-phosphate-dextrose (CPD) and citrate-phosphate-dextrose-adenine (CPDA) solutions that increased shelf life to 35 days and 42 days respectively. More recently, additive solutions containing saline, adenine, and dextrose have been developed to augment red cell survival following transfusion, although without any direct increase in storage duration. It is now well appreciated, however, that a number of morphologic and biochemical changes occur during red cell storage prior to product expiry, and these changes may hinder erythrocyte viability and function following transfusion. Despite a relatively large body of literature detailing the metabolic and structural deterioration that occurs during red cell storage, evidence for a significant detrimental clinical effect related to the transfusion of older blood is relatively less conclusive, limited primarily to observations in retrospective studies. Nonetheless, the implication that the transfusion of old, but not outdated blood may have negative clinical consequences demands attention. The purpose of this report is to describe the current understanding of the biochemical and structural changes that occur during storage, known collectively as the storage lesion, and to critically review the clinical evidence concerning the detrimental consequences associated with the transfusion of relatively older red cells.