Anemia treatment in nondialysis chronic kidney disease (ND-CKD) and dialysis CKD patients (D-CKD) has been recently scrutinized in the literature and by the lay press. New evidence suggests that patients receiving epoetin and achieving higher hemoglobin have a higher risk of death and cardiovascular complications. Data from the Centers for Medicare & Medicaid Services demonstrate upward spiraling costs of injectables, especially epoetin, in the care of CKD patients. There is considerable literature favoring the use of subcutaneous administration of epoetin compared to intravenous route in hemodialysis patients. Evidence clearly shows that the subcutaneous route achieves the target hemoglobin level at a lower administered dose. Thus, the same clinical effect can be achieved at a lower cost. Despite the economic and evidentiary justifications for subcutaneous administration of epoetin, adoption of this strategy has been limited, especially in the United States. Reasons include: inflexibility by dialysis providers because of reduced profitability, claims that patients oppose the subcutaneous route because of pain at the site of injection, concerns regarding pure red cell aplasia associated with subcutaneous administration, and greater hemoglobin cycling with the subcutaneous route. In this article, the advantages and disadvantages of the subcutaneous route are reviewed.