Peptic ulcer bleeding is a frequent and dramatic event with both a high mortality rate and a substantial cost for healthcare systems worldwide. It has been found that age is an independent predisposing factor for gastrointestinal bleeding, with the risk increasing significantly in individuals aged>65 years and increasing further in those aged>75 years. Indeed, bleeding incidence and mortality are distinctly higher in elderly patients, especially in those with co-morbidities. NSAID therapy and Helicobacter pylori infection are the most prevalent aetiopathogenetic factors involved in peptic ulcer bleeding. The risk of bleeding seems to be higher for NSAID- than for H. pylori-related ulcers, most likely because the antiplatelet action of NSAIDs impairs the clotting process. NSAID users may be classified as low or high risk, according to the absence or presence of one or more of the following factors associated with an increased risk of bleeding: co-morbidities; corticosteroid or anticoagulant co-therapy; previous dyspepsia, peptic ulcer or ulcer bleeding; and alcohol consumption. Different types of NSAIDs have been associated with different bleeding risk, but no anti-inflammatory drug, including selective cyclo-oxygenase (COX)-2 inhibitors, is completely safe for the stomach. Furthermore, even low-dose aspirin (acetylsalicylic acid) [<325 mg/day] and a standard dose of non-aspirin antiplatelet treatment (clopidogrel or ticlopidine) have been found to cause bleeding and mortality. No clear risk factor favouring H. pylori-related ulcer bleeding has been identified. Peptic ulcer bleeding prevention remains a challenge for the physician, but data are now available on use of a safer and cheaper strategy for both low- and high-risk patients. Unfortunately, despite the fact that several society and national guidelines have been formulated, these are poorly followed in clinical practice. Proton pump inhibitor (PPI) or misoprostol therapy and H. pylori eradication in NSAID-naive patients are the most commonly proposed strategies. Selective COX-2 inhibitor therapy in high-risk patients has also been suggested, but concerns over the possible cardiovascular adverse effects of some of these agents should be taken into account. Moreover, switching to selective COX-2 inhibitors in patients with previous bleeding is not completely risk free, and concomitant PPI therapy is also needed. H. pylori eradication is mandatory in all patients with peptic ulcer, and such an approach has been found to be significantly superior to PPI maintenance therapy. H. pylori eradication is frequently achieved with sequential therapy in elderly patients with peptic ulcer. In conclusion, upper gastrointestinal bleeding is a dramatic event with a high mortality rate, particularly in the elderly. Some effective preventative strategies are now available that should be implemented in clinical practice.