For more than 15 years recombinant human erythropoietin (r‐HuEPO) has been used for the treatment of renal anemiabenefiting patients with improved quality of life and reduced need for blood transfusions. It is still early in the history of r‐HuEPO treatment; therapy has changed little and there have been few investigations into whether current treatment strategies are optimal. Of notecurrent therapy makes little attempt to mimic normal erythropoietin biology. Large doses of drug are administered episodicallyresulting in great fluxes in serum erythropoietin levels. It is unlikely that this approach is very efficient from the erythropoietic standpoint. Furthermorethe effects of these nonbiologic kinetics on extraerythroid organs that express erythropoietin receptors are unknown. In this reviewthe current state of r‐HuEPO treatment is compared to the normal biology of erythropoietin and potential pitfalls caused by divergences are explored.