Despite increasing use of targeted therapies to treat cancer, anemia remains a common complication of cancer therapy. Physician concerns about the safety of intravenous (IV) iron products and erythropoiesis-stimulating agents (ESAs) have resulted in many patients with cancer receiving no or suboptimal anemia therapy. In this article, we present four patient cases illustrating both common and complex clinical scenarios. We first present a review of erythropoiesis, then describe our approach to cancer anemia by identifying contributing causes before selecting specific treatments. We summarize clinical trial data affirming the safety and efficacy of currently-available IV iron products used to treat cancer anemia, and illustrate how we use commonly-available laboratory tests to assess iron status during routine patient management. We compare adverse event rates associated with IV iron versus red cell transfusion and discuss using front-line IV iron monotherapy to treat anemic patients with cancer, decreasing the need for ESAs. A possible mechanism behind ESA-induced tumor progression is discussed. Finally, we review the potential of novel therapies such as ascorbic acid, prolyl hydroxylase inhibitors, activin traps, hepcidin and bone morphogenetic protein antagonists, in treating cancer anemia.