Iron deficiency anemia is common worldwide. In adult patients without inflammation, a ferritin level of less than 45 ng/mL or ferritin level of 46 to 99 ng/mL plus a transferrin saturation of less than 20% is diagnostic of iron deficiency. In patients with inflammation, a ferritin level of less than 100 ng/mL is diagnostic. Risk factors for iron deficiency anemia include low socioeconomic status, female sex, age younger than 5 years, and chronic inflammation. Underlying causes should be investigated. Recurrent blood loss is responsible for 94% of cases. In younger patients with a plausible cause of iron deficiency anemia (eg, heavy menstrual bleeding), a reasonable approach is to treat the bleeding and provide iron supplementation. In men and postmenopausal women, bidirectional endoscopy should be performed. Noninvasive testing for Helicobacter pylori infection and celiac disease is recommended because both are common causes of iron deficiency anemia. Oral iron replacement is the first-line treatment for most patients. However, intravenous iron is recommended in patients with heart failure to increase exercise capacity. Every-other-day dosing of oral iron improves absorption. Approximately 50% of patients have decreased adherence due to adverse effects. Patients taking oral iron therapy should be evaluated for response in 2 to 4 weeks. Patients who cannot tolerate oral iron or do not have adequate response should receive intravenous iron. Hypersensitivity to newer formulations of intravenous iron is rare (less than 1%).