Red blood cell transfusion therapy has been used with the ultimate goal of enhancing oxygen delivery to vital organs and tissue beds, thus enhancing cellular function. Red blood cell transfusion therapy is also a long-standing practice, and since the 1950s it has only grown in utilization, especially within the United States. Recently, transfusion therapy has come under increased scrutiny with a desire to develop evidence-based therapeutic guidelines that not only decrease undue risk to the patient but also decrease the overutilization of this high-cost, low-availability product. Despite the development and implementation of these guidelines, significant complications associated with red cell therapy persist and may be related to storage of blood products. Recently, within the transfusion literature, there has been a renewed focus on red cell storage lesions and their contributions to perioperative outcomes. Several meta-analyses, and now a recently launched, multinational randomized controlled trial, have been initiated to help bring clarity to whether or not the length of product storage has any effect on patient outcomes. This review will focus on the nature of storage lesions, complications associated with storage, as well as a brief review of some of the more provocative literature surrounding this controversial topic.