Critically ill patients are prone to stress-induced ulcerations in the upper gastrointestinal tract, which might lead to life-threatening bleeding. Therefore, an effective stress ulcer prophylaxis is absolutely indicated and H2-blocking agents, anticholinergics, antacids, sucralfate, enteral nutrition and prostaglandin E analoges are recommended. H2-blocking agents seem to provide effective prophylaxis, but severe side effects seem to limit their application. Most of all, as they are less effective as antacids and as they cause considerable costs. Additionally H2-blocking agents elevate gastric pH, thereby favouring microbic colonisation of gastric juice. Microorganism from gastric juice may reach the tracheobronchial system and lead to nosocomial pneumonias. The contaminated gastric juice may also be considered as endogenous source for sepsis and entero-colitis. The anticholinergic agent pirenzepine does not increase gastric pH and seems to be effective in neurological and neurosurgical intensive care patients. Antacids are effective in stress ulcer bleeding prophylaxis, but favour bacterial overgrowth, are badly tolerated by patients and cause a high amount of nursing time. Sucralfate seems to be as effective as antacids, is better tolerated and does not elevate gastric pH. The remaining acidity of gastric juice blocks bacterial contamination. After all, the smallest costs of effective stress ulcer prophylaxis, makes sucralfate to the medicament of first choice. However, in severely ill patients, a combined stress ulcer prophylaxis with two or more agents seems to be necessary.