Helicobacter pylori is now considered a major pathogen of the upper gastrointestinal tract. It is seen as an important cause of peptic ulceration not associated with NSAID use. It is also increasingly linked to other diseases of the GI tract, although the relationship between the organism and conditions such as gastric cancer, non-ulcer dyspepsia and gastroesophageal reflux disease is not as clear as is the case in peptic ulcer disease. This is probably because of a lack of well-performed, statistically powerful, prospective therapeutic trials that indicate that H. pylori eradication is of benefit in these diseases. The high infection rate without overt disease seen in many populations, especially from developing countries, probably contributes to this "credibility gap." While we have excellent therapeutic regimens available at this time, rational targeting requires that the objective evidence in favor of therapeutic intervention in upper GI disease, as well as the local H. pylori epidemiology, needs to be considered.