Helicobacter pylori infection continues to be one of the hottest topics in gastroenterology, challenging the primary care physician daily with the clinical application of its new developments and frequency of involvement in differential diagnosis. This article offers the primary care physician a practical approach to the dyspeptic office patient that emphasizes the differential diagnosis of H pylori. Included is a strategy for rapid patient evaluation through key questions in the history, simple maneuvers in the physical examination, and a logical approach to testing and therapy based on the latest literature. The recommendations for all these office-based steps are designed to be efficient, cost-effective, and clinically relevant.