Anemia has a high prevalence and incidence in patients with cancer and is associated with a range of symptoms, including fatigue, which affect the vast majority patients receiving chemotherapy exerting a considerable impact on patients' quality of life. The development of the erythropoiesis-stimulating agent epoetin represented a major step forward in the treatment of chemotherapy-related anemia, providing an effective and safe alternative to red blood cell transfusions. The subsequently introduced epoetin analogue, darbepoetin alpha, with a prolonged serum half-life, allowed for extended dosing intervals and less frequent administration. Recently published large prospective trials provided the oncology community with new important information on the use of currently available erythropoietic agents to improve anemia in patients suffering from cancer. However, it is also clear from recent reports that scrutiny on the safe use of these drugs is still required.