Helicobacter pylori is a common bacterial pathogen responsible for substantial gastrointestinal morbidity worldwide. Helicobacter pylori infection can be clinically challenging, given the numerous diagnostic and therapeutic options available. In this article, we provide a systematic review of H pylori epidemiology and pathogenesis. In addition, we provide a simplified approach to the diagnosis and treatment of H pylori infection, suitable for application in the primary care setting. On completion of this article, one should be able to (1) state the indications for H pylori testing; (2) identify noninvasive and invasive tests to diagnose H pylori infection; and (3) describe the advantages and disadvantages of various treatment regimens.