Recombinant human erythropoietin (r HuEPO) therapy is expensive, and it is therefore important to optimize its use to satisfy the health economist as well as the prescriber. Five main issues can be considered in helping to achieve this goal: (i) Route and site of administration. Much evidence suggests that subcutaneous (s.c.) administration of r-HuEPO is more cost-effective than intravenous (i.v.) administration, i.e. lower s.c. doses may be used to achieve the same effect. There are, however, some studies which suggest that there is little to choose between the two routes. One pharmacokinetic study in normal volunteers found that s.c. injection of r-HuEPO into the thigh resulted in greater peak values and greater bioavailability than s.c. injection into the arm or abdomen. (ii) Frequency of injection. There are now reports of dialysis patients being variously treated with once-weekly, twice-weekly, thrice-weekly, and once-daily s.c. administration of r-HuEPO. Despite some comparative studies, the optimum dosing frequency for s.c. r-HuEPO remains unclear. (iii) Iron status. Failure of an adequate supply of iron to the erythron is probably the most common and most easily treated cause of sub-optimal response to r-HuEPO. Effective and regular monitoring of iron status by measurement of serum ferritin, transferrin saturation, and per cent hypochromic red cells is critical to the management of the patient receiving r-HuEPO, and there is increasing evidence that liberal use of i.v. iron may enhance the response to this treatment. (iv) Other factors affecting response to r-HuEPO. Several other factors or conditions can modulate the response to r-HuEPO and these must be recognized and corrected in order to optimize the use of this drug. (v) Target haemoglobin. There is considerable debate regarding the target haemoglobin which should be aimed for in order to maximize improvements in quality of life and cardiac function. To date, a target of 10–12 g/dl has often been used; aiming for a higher haemoglobin undoubtedly requires larger doses of r-HuEPO, and it is not known whether the increased cost is matched or justified by parallel improvements in quality of life or cardiac function in the long-term.