Iron deficiency anemia is the most common form of anemia encountered in clinical practice and is an extremely common manifestation of chronic occult gastrointestinal bleeding. Current evidence suggests that a large proportion of men and postmenopausal women with iron deficiency anemia harbor significant gastrointestinal tract pathological lesions as the source of blood loss. As such, the evaluation of patients with iron deficiency anemia is generally focused on the gastrointestinal tract. Importantly, the diagnosis of iron deficiency anemia should be firmly established before an extensive evaluation is undertaken. Management strategies for patients with iron deficiency anemia are reviewed; an important general point is that clinical features (ie, symptoms) may help direct specific investigation. The role of small-intestinal investigation in patients with iron deficiency anemia is controversial and should probably be reserved for patients with iron deficiency anemia and persistent gastrointestinal symptoms or those who fail to respond to appropriate therapy. The treatment and prognosis of patients with iron deficiency anemia and the majority of gastrointestinal tract lesions are straightforward. However, patients with vascular ectasias as the source of blood loss can represent a true management challenge.