There has been a dramatic sea change in the use of erythropoiesis-stimulating agents (ESAs) for anemic persons with chronic kidney disease (CKD) or cancer patients undergoing chemotherapy. An important area that has not been addressed previously is a CKD patient who also has a malignancy. Clinical guidelines exist that outline recommended treatments for each disease, but the intersection of the two disease processes presents difficult decisions for patients and physicians. Herein, we review the background underlying recent revisions in clinical alerts and guidelines for ESAs, and provide guidance for treating anemia among CKD patients who are receiving no therapy, chemotherapy with curative intent, or chemotherapy with palliative intent. The guiding principle is that comprehensive assessment of risks and benefits in the relevant clinical setting is imperative.