Preservation and long-term storage of red blood cells (RBCs) is needed to ensure a readily available, safe blood supply for transfusion medicine. Effective preservation procedures are required at various steps in the production of a RBC product including testing, inventory, quality control, and product distribution. Biopreservation is the process of maintaining the integrity and functionality of cells held outside the native environment for extended storage times. The biopreservation of RBCs for clinical use can be categorized based on the techniques used to achieve biologic stability and ensure a viable state after long-term storage. This paper will review the history, science, current practices, and emerging technologies of current RBC biopreservation approaches: hypothermic storage, cryopreservation, and lyophilization.