Erythropoiesis-stimulating agents (ESAs) have been used to manage anemia in chronic kidney disease (CKD) to reduce transfusion requirements and anemia symptoms. Lack of objective benefit of normalizing hemoglobin (Hb) levels and increased evidence of ESA-induced complications in persons with anemia has resulted in clinicians generally attempting to maintain Hb levels in the 10- to 11-g/dL range. In 2000, concerns in patients with cancer arose attributable to associations of ESA use with increased mortality, thrombotic complications, and cerebrovascular accidents led to a change in US Food and Drug Administration oncology guidelines regarding limitation of ESA use for chemotherapy-induced anemia. No guidance was rendered for individuals with CKD and cancer. Persons with CKD with remote or active malignancy should receive the lowest ESA doses possible that achieve a maximum Hb level of 10g/dL. Based on current data, although ESAs may promote progression or worsen outcomes in some cancers, we lack data that ESAs increase the likelihood of developing new cancers in patients on dialysis or earlier stages of CKD.