Among the gastrointestinal emergencies, acute upper gastrointestinal bleeding (UGIB) remains a challenging clinical problem owing to significant patient morbidity and costs involved with management. Peptic ulcer bleeding (PUB) contributes to the majority of causes of UGIB with a growing concern of its impact on the elderly and the increasing use of NSAIDs as precipitating bleeding episodes. Apart from initial critical assessment and care, endoscopy remains as the preferred initial management of PUB. Early use of high-dose proton pump inhibitor therapy is cost-effective and reduces the need for endotherapy as well as rebleed rates. Current endoscopic modalities offer a wide range of choices in high-risk PUB (active arterial bleeding or non-bleeding visible vessel). A combination of injection (epinephrine) along with thermal or endoclips therapy offers the best strategy for overall successful clinical outcomes. The role of endotherapy for adherent clots is controversial. A second-look endoscopy may be beneficial in high-risk patients. A multidisciplinary team approach should be part of all treatment protocols for the ideal management of UGIB. Copyright © 2010 S. Karger AG.