The interaction between Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) in ulcerogenesis has been visited by many studies. Apparently these studies yielded conflicting results. This is a result of a wide diversity of methodology, selection of patient groups and definitions of outcome used by different investigators. This review attempts to analyse separately studies dealing with new or chronic NSAID users, primary or secondary prophylaxis, complicated or uncomplicated ulcers in NSAID or aspirin users. Evidence suggests that eradication of Helicobacter pylori infection may reduce the risk of ulcer and ulcer complications in patients requiring NSAIDs and aspirin. Whether or not one should test-and-treat H. pylori before prescribing NSAIDs is a complicated issue. Factors such as the ulcer risk of patients, previous history of NSAID usage and the use of aspirin or NSAIDs would guide the strategy.