Upper gastrointestinal bleeding from peptic ulcers or other nonvariceal causes generally stops spontaneously; if it fails to do so, aggressive management is required. Such measures also are necessary for patients at high risk for rebleeding. Endoscopic therapy achieves hemostasis in >90% of bleeding patients and reduces mortality. After successful hemostasis of the initial bleeding episode, the primary concern becomes the prevention of rebleeding, which occurs in up to 20% of patients. Acid suppression with histamine-2-receptor antagonists has been widely used for many years to prevent recurrent bleeding. However, in acutely bleeding patients, these agents have not been shown to reduce the number of episodes of further bleeding or rebleeding or to reduce the need for transfusions or surgery. Omeprazole, an intravenous proton pump inhibitor, significantly reduced the rate of rebleeding in a recent placebo-controlled trial in which only patients with endoscopic confirmation of successful hemostasis were enrolled. Although this drug does not seem to reduce the need for surgical intervention or to decrease mortality, the trial does indicate the promise of intravenous proton pump inhibitors in reducing upper gastrointestinal bleeding. Evidence from additional well-controlled trials is needed to confirm this finding. The use of proton pump inhibitors in this setting also may have a positive economic impact, and a decrease in the percentage of patients who experience rebleeding will eliminate the cost of further management strategies in those cases.