Obscure gastrointestinal bleeding (OGIB) is defined as an intermittent or continuous loss of blood in which the source has not been identified after upper endoscopy and colonoscopy. It constitutes a diagnostic and therapeutic challenge for the general internist and the gastroenterologist. This article provides an overview of the etiology, clinical presentation, and diagnostic modalities of OGIB including push enteroscopy, double balloon enteroscopy, wireless capsule endoscopy, enteroclysis, angiography, bleeding scanning with labeled red blood cells, and surgery with intraoperative enteroscopy. Therapeutic modalities including iron replacement, combined hormones, octreotide acetate, therapeutic endoscopy, and surgery are also discussed. In addition, a rational approach to patients with OGIB according to the clinical presentation is presented herein.