Erythropoietic agents have transformed the management of renal anaemia. Two forms of recombinant human erythropoietin (rHuEPO) have been available since the early 1990s, and more recently, a second-generation erythropoietic agent, darbepoetin alfa, has been granted a licence for treating this condition. The endogenous erythropoietin molecule may contain anything from 4 to 14 sialic acid residues. The various isoforms have different biological potencies in vivo owing to their different metabolic clearance rates. However, there is a continuing debate about those organs potentially involved in the metabolism of the erythropoietin molecule; the kidneys, liver, and bone marrow have all been suggested as possible participants. Darbepoetin alfa contains two extra N-linked glycosylation consensus sequences increasing the potential maximum number of sialic acid residues from 14 up to 22. In vitro, the affinity of darbepoetin alfa for the erythropoietin receptor is less than for the natural ligand, but this is more than compensated for by the increased potency in vivo. One of the most important factors determining the biological activity of erythropoiesis-stimulating agents is the length of time that the serum concentration of the protein remains above the threshold necessary for erythropoiesis. The pharmacokinetic profile of darbepoetin alfa is distinct from that of rHuEPO, the major difference being the much longer elimination half-life and slower clearance in vivo of darbepoetin alfa leading to prolonged erythropoietic activity. Stimulation of erythropoiesis depends both on an ambient circulating level of erythropoietin and on the mechanisms governing the interaction of the hormone with its receptor. Our knowledge regarding the latter is limited and it is difficult to predict the optimum frequency of administration for an erythropoietic agent. In general, rHuEPO is given two or three times weekly. A small number of studies have supported the once-weekly use of rHuEPO. All clinical trials so far conducted on darbepoetin alfa have demonstrated success with once-weekly and once every other week dosing.