Recombinant human erythropoietin (r-HuEPO) is a new therapeutic modality for the treatment of neonatal anemia. The results of three large controlled trials were published within the past year. This article reviews the physiologic rationale underlying the use of r-HuEPO in preterm infants, addresses how the design of clinical trials affects outcomes and conclusions, and discusses the recent trials in this context. The article concludes with a summary of questions that require further investigation.