BACKGROUND Prior to the approval of the first erythropoiesis-stimulating agent (ESA) in the early 1990s, red blood cell transfusions were the primary means of treating severe chemotherapy-induced anemia (CIA), with little recourse for those with more mild forms of the condition. The introduction of the ESAs allowed treatment of mild-to-moderate CIA in patients with cancer. It has been a decade since darbepoetin alfa (DA), a second-generation ESA with a longer half-life, became available to patients with CIA. OBJECTIVE We present a review of studies on DA in CIA, from its development through to the present day. Medline was searched for randomized clinical trials on DA. Additional trials and meta-analyses on ESAs were incorporated into this review when relevant. RESULTS The first publications on DA generally focused on optimal dosing, efficacy and tolerability. In these, it was shown that DA is an effective and well tolerated treatment option to achieve hematopoietic response, regardless of dosing interval. Subsequently, the focus shifted towards meta-analyses on survival data of all ESAs. These reported conflicting results regarding mortality and/or disease progression. However, guidelines for ESA use were updated and, when followed, these make ESAs a well tolerated and effective tool for managing CIA. CONCLUSIONS As the past decade has broadened our knowledge on the benefits and risks of CIA management, continued high-quality studies will help to optimize treatment with ESAs in order to maximize quality of life for these patients. The limitation of a literature review of this nature is the complete reliance on previously published research and the availability of these studies using the methodology outlined above.