Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used and therapeutically effective groups of drugs in the Western world. However, gastrointestinal problems constitute all too frequently reported unwanted effects of NSAIDs; their effects on the gastric (and intestinal) mucosa are, therefore, well documented. A review of the evidence suggests that NSAID-induced gastric damage occurs as a result of a dual insult, by NSAID-mediated direct (and indirect) acidic damage followed almost simultaneously by the deleterious (systemic) effect of prostaglandin inhibition. A number of strategies have been used in the management of NSAID-induced gastric damage; however, not all have been entirely successful. Nonetheless, a number of approaches have met with a considerable amount of success, including direct gastroprotection, enhancement of mucosal defence mechanisms and, perhaps most encouragingly, the development of newer NSAIDs which display not only considerable clinical efficacy but a reduced gastrointestinal adverse event profile.