We have sufficient knowledge of the biology of hematopoietic stem cells to hope that we might generate human red blood cells in the laboratory. It may soon be possible to produce enough to transfuse "cultured" red blood cells to manufacture human red blood cells from hematopoietic stem cells for transfusion purposes. This article describes progress and the challenges that remain in the search for in vitro generated red blood cells that can be efficiently manufactured in high volumes and given to any recipient.