In patients with chronic kidney disease (CKD), sensitivity to recombinant human erythropoietin (r-HuEPO, epoetin) is of clinical and economic importance. Insight into factors that influence sensitivity and response to epoetin is essential for the adequate management of anaemia. Some factors influencing response to epoetin, such as gender, age, length of time on dialysis, type of dialysis and co-morbidities such as haemoglobinopathy, are not susceptible to clinical intervention. However, many other factors can be controlled. Iron deficiency is the most common factor that limits the response to epoetin. Adequate monitoring of iron status and iron supplementation in patients with CKD will result in a more efficient epoetin response. Increased dialysis dose is associated with improvements in haemoglobin outcome and reduced requirements for epoetin. Dialysis water quality (both chemical and biological) is also important in determining the response to epoetin: 'ultrapure' water reduces epoetin requirements. Some patients, despite adequate epoetin and iron therapy, still have epoetin resistance (low haemoglobin and/or high epoetin requirements). Raised C-reactive protein and/or low albumin may reflect long-standing inflammatory pathology and indicate a need for investigation.