Mucosal lesions are observed in 40 to 100% of critically ill patients. They are mainly due to gastric acid hypersecretion, biliary reflux, a decrease in mucosal defences, and digestive mucosal ischaemia. Acute upper gastrointestinal bleeding in intensive care unit (ICU) patients may occur, and if severe is associated with increased mortality and hospitalization costs. However, progress in the ICU management of patients, and especially in nutritional support, probably explains the low incidence of stress-induced gastrointestinal bleeding. Preventive strategies are indicated in high risk patients, i.e. when the risk of gastrointestinal bleeding is above 1%. Risk factors are not well defined presently, and probably include defective haemostasis and/or respiratory failure requiring prolonged ventilation assistance. Gastric hypersecretion can be well controlled with anti-H2 agents and sucralfate; these treatments improve the rate of complications but do not reduce overmortality related to gastrointestinal bleeding. Other drugs such as omeprazole are under investigation but due to insufficient clinical data and excessive cost, omeprazole cannot be recommended for this use. In addition, enteral nutritional support per se may efficiently prevent stress ulcers. Eradication of Helicobacter pylori has never been evaluated in this context. The selection of drugs today depends not only on efficacy and on costs, but also on possible adverse effects such as the putative risk of nosocomial pneumonia due to gastric bacterial overgrowth. Finally, only careful medico-economic evaluations of stress ulcer prophylaxis in ICUs will permit the implementation of valuable practice guidelines.