Dyspepsia, defined as pain or discomfort centered in the upper abdomen, is a common clinical problem. A variety of underlying disease states may result in dyspepsia, but commonly, diagnostic investigation will show no identifiable pathology, and the patient is diagnosed with nonulcer dyspepsia. Numerous hypothesis have been suggested as to the cause of symptoms in patients with nonulcer dyspepsia, including perturbations of gastroduodenal motility, hypersensitivity to physiologic stimuli including acid, and the effect(s) of infection within the gastric mucosa by Helicobacter pylori. Some epidemiological studies have suggested that patients with nonulcer dyspepsia may have a slightly higher prevalence of H. pylori infection. However, association does not prove causation. Causation of nonulcer dyspepsia by H. pylori could best be documented by resolution of symptoms following eradication of the infection. Early intervention studies indicated that there was a beneficial effect on symptoms of nonulcer dyspepsia with H. pylori eradication, but most of these studies had serious methodological flaws. In the last few years there have been a number of well-designed studies investigating the effect of H. pylori eradication on symptoms in patients with nonulcer dyspepsia. The results of these studies are inconsistent, but suggest that there is little, if any benefit from treatment. This case-based article on nonulcer dyspepsia discusses these studies in detail and provides a possible explanation for the differences in outcomes.