The development of capsule endoscopy and double-balloon enteroscopy has increased diagnostic and therapeutic rates in obscure gastrointestinal hemorrhage, where angiodysplasia of the small bowel is the most frequent cause. Nevertheless, almost 25-40% of patients who are not candidates or do not respond to endoscopic, angiographic, or surgical management may be at high risk of rebleeding, and therefore lack a clearly effective medical therapy. The utility of hormonal therapy remains unclear and is burdened by adverse effects. Subcutaneous octreotide usually controls bleeding but does not seem adequate for maintenance therapy. Non-selective beta-blockers alone or in combination with other treatments, as in the prophylaxis of portal hypertension variceal bleeding, may be helpful. Recently, octreotide LAR, a depot formulation administered once a month intramuscularly, and oral thalidomide, a powerful inhibitor of angiogenesis, have demonstrated their effectiveness and safety for long-term therapy in anecdotal case reports and deserve further investigation.