Patients receiving recurring blood transfusions as supportive therapy to treat chronic anemias, such as myelodysplastic syndromes, thalassemia, and sickle-cell disease, are at risk of iron accumulation. The clinical consequences of iron overload are progressive liver damage, cardiac disease, and endocrine disorders, which can be fatal. Nurses have a vital role in the initial assessment and monitoring of patients undergoing transfusion therapy and their ongoing care. Iron levels may be managed effectively with iron chelation therapy, and treatment guidelines recommend initiation when serum ferritin levels reach more than 1,000 mcg/L. Deferoxamine has been used effectively in clinical practice for more than 40 years. Newer agents, such as deferasirox, have introduced the option of oral therapy to manage iron overload. Those agents and practical management of patients receiving multiple blood transfusions are discussed.