Several major management guidelines on dyspepsia (upper abdominal pain or discomfort) recommend an initial 'test-and-treat' policy (non-invasive Helicobacter pylori testing with eradication therapy if positive) in uninvestigated patients less than about 45 years old. However, the evidence that this is the optimal strategy is limited. Data from the few available randomized controlled trials provide evidence that this policy improves symptomatology more than a 'test-and-endoscope' approach (in which only H. pylori-positive patients undergo early endoscopy) in those with upper abdominal pain. The balance of cost-effectiveness data from clinical studies and decision analyses indicates that both 'test-and-treat' and empirical anti-secretory therapy approaches are more cost-effective than the 'test-and-endoscope' strategy. Therefore, given concerns about the safety of widespread H. pylori eradication, initial empirical anti-secretory therapy may be a cost-effective alternative to the 'test-and-treat' policy in some younger dyspeptic patients. The effectiveness of such an empirical approach might well be improved by symptom-guided therapy and there is growing evidence that the predominant dyspeptic symptom may provide this guide. The diagnostic, therapeutic and economic utility of this approach merits further clinical investigation.