Acute upper gastrointestinal bleed (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 non-steroidal anti-inflammatory drugs as precipitating bleeding episodes. Apart from initial critical care, endoscopy is the preferred first-line management of PUB. Early use of empirical high-dose proton pump inhibitor therapy prior, during and after endoscopy is cost-effective and reduces the need for endotherapy. Current endoscopic modalities, both thermal and non-thermal, offer a wide range of choices in high-risk PUB (active arterial bleeding or non-bleeding visible vessel). Combinations of injection (epinephrine) along with thermal therapy or endoclips are recommended for better 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 © 2009 S. Karger AG.