Dyspepsia is a chronic or recurrent pain or discomfort centered in the upper abdomen; patients with predominant or frequent (more than once a week) heartburn or acid regurgitation, should be considered to have gastroesophageal reflux disease (GERD) until proven otherwise. Dyspeptic patients over 55 yr of age, or those with alarm features should undergo prompt esophagogastroduodenoscopy (EGD). In all other patients, there are two approximately equivalent options: (i) test and treat for Helicobacter pylori (H. pylori) using a validated noninvasive test and a trial of acid suppression if eradication is successful but symptoms do not resolve or (ii) an empiric trial of acid suppression with a proton pump inhibitor (PPI) for 4-8 wk. The test-and-treat option is preferable in populations with a moderate to high prevalence of H. pylori infection (> or =10%); empirical PPI is an initial option in low prevalence situations. If initial acid suppression fails after 2-4 wk, it is reasonable to consider changing drug class or dosing. If the patient fails to respond or relapses rapidly on stopping antisecretory therapy, then the test-and-treat strategy is best applied before consideration of referral for EGD. Prokinetics are not currently recommended as first-line therapy for uninvestigated dyspepsia. EGD is not mandatory in those who remain symptomatic as the yield is low; the decision to endoscope or not must be based on clinical judgement. In patients who do respond to initial therapy, stop treatment after 4-8 wk; if symptoms recur, another course of the same treatment is justified. The management of functional dyspepsia is challenging when initial antisecretory therapy and H. pylori eradication fails. There are very limited data to support the use of low-dose tricyclic antidepressants or psychological treatments in functional dyspepsia.