Biosimilars have been developed for several biologic therapeutic agents, including erythropoiesis-stimulating agents (ESAs). However, biosimilars cannot be assumed to be completely identical to the reference product, nor can two different biosimilars of the same reference product be considered equivalent. Accordingly, standards for approving biosimilars are distinct from those for generic versions of conventional pharmaceuticals.By late 2007, two biosimilar epoetins (HX575 and SB309) had been approved by the European Medicines Agency (EMA), following a series of pharmacokinetic and pharmacodynamic equivalence studies, as well as phase 3 clinical comparability evaluations. Additionally, the results of a limited number of postauthorization interventional or observational studies and quality comparisons were published subsequently on both products.The reported differences in glycosylation profiles between these epoetin biosimilars and their reference product, as well as the lack of long-term safety and efficacy evaluation, could indicate a need to develop a more comprehensive analysis of the available data, and to evaluate the post-authorization real-life data, in order to gain a better understanding of any potential implications of molecular structural or formulation differences on longterm safety and effectiveness.Switching between an original reference ESA and a biosimilar (and possibly also switching between biosimilar versions of the same product) should be regarded as a change in clinical management. Clinicians need to be fully involved in such decisions. Prescribing by brand name will prevent unintentional substitution by pharmacists and allow for effective pharmacovigilance, in accordance with recent EU directives. In this review, the authors have analyzed most of the published information on the two epoetin biosimilars, HX575 and SB309, to highlight the points that healthcare providers may need to consider when assessing an epoetin biosimilar.