The fact that nonsteroidal anti-inflammatory drugs (NSAIDs) damage the gastroduodenal mucosa is no longer contested. Endoscopic studies in normal volunteers after NSAID administration have failed to predict which NSAIDs would be safest when administered chronically. NSAID use has been associated with a disproportionately high frequency of upper gastrointestinal bleeding and perforation of ulcers. All of the newer NSAIDs appear to be similar in their propensity to cause mucosal damage, including peptic ulceration. On any given day, more than 10% of patients receiving NSAIDs chronically will have a gastric ulcer, a point prevalence of ulcer disease at least 5 to 10 times higher than in patients who are not taking NSAIDs. The dose-response relationship between anti-inflammatory activity and untoward events, coupled with increased use of newer more potent NSAIDs, explains, in part, the increased incidence of NSAID-associated ulcer complication of bleeding and perforation. The possible association of the increase in prevalence of Campylobacter pylori gastritis with aging and the apparent increase in NSAID-associated complications in the elderly is discussed. The current status of nonsteroidal drug therapy can be summarized as follows: 1) new NSAIDs are not safer than the old NSAIDs, as far as major gastrointestinal side effects are concerned, 2) NSAIDs should be avoided when analgesia is the main goal, 3) if NSAIDs are required, the lowest possible dose that achieves pain relief should be used, 4) newer NSAIDs available only in relatively high anti-inflammatory activity dosages should be restricted to those patients in whom high levels of anti-inflammatory activity are desired.