Dyspepsia and gastroesophageal reflux disease are common conditions in clinical practice. Current management strategies emphasize testing and treatment for Helicobacter pylori in the initial management of patients presenting with dyspeptic symptoms in regions where the prevalence of H. pylori infection is >15%. Population-based studies in patients with dyspepsia suggest that peptic ulcer disease related to H. pylori infection is decreasing in prevalence, whereas gastroesophageal reflux disease is becoming a more common cause of dyspeptic symptoms. Unfortunately, symptoms are a poor predictor of endoscopic findings, and alarm features are not a good predictor of an underlying malignancy. Although peptic ulcer disease has declined in Western countries, specific populations such as immigrants and rural communities may have a high prevalence of infection and peptic ulcer disease that needs to be considered in initial dyspepsia management, even in areas where the general prevalence of H. pylori infection has declined below 15%.