Anti-secretory drug use is common in patients with uninvestigated and functional dyspepsia, but the value of such agents has been controversial. Four large studies have evaluated the symptomatic outcome after a short course of acid inhibition in patients with uninvestigated dyspepsia presenting in primary care. All of these studies demonstrated a superior symptom response to proton pump inhibitor therapy compared with placebo and acid-alginates or H-2-receptor antagonists. In patients with documented functional dyspepsia, 17 parallel group trials have evaluated an H-2-receptor antagonist against placebo, with mixed results. A recent Cochrane review based on eight controlled trials concluded that there was a significant benefit of H-2-blockers over placebo with a relative risk reduction of 30%, but as gastro-oesophageal reflux disease was nor, excluded, the conclusions are questionable. Six controlled studies have compared symptom relief after a short course of proton pump inhibitor therapy compared with placebo. Overall, there does appear to be a therapeutic gain with proton pump inhibitors over placebo, although how much of this is explained by undiagnosed gastro-oesophageal reflux disease remains unclear. There is conflicting evidence on the value of symptom subgrouping as a predictor of response to acid suppression. Overall, there is little convincing evidence that Helicobacter pylori infection influences the therapeutic outcome of acid-suppressant therapy. In conclusion, there appears to be a subgroup of patients with functional dyspepsia who will respond to acid suppression over and above placebo, but further work is required to characterize these responders.