Red blood cells, currently obtained from donors, represent the most common form of cell-based therapy. A better understanding of normal erythropoiesis is leading to improved multi-step protocols for the in vitro generation of fully mature red cells. The extensive in vitro expansion of embryonic erythroblasts and development of erythroid precursors as a potential transfusion product may help to deal with issues of scale and eventually find a place in the treatment of patients with acute and chronic anemias.