Patients with dyspepsia may present with associated complaints of abdominal pain, bloating, fullness, acid reflux, and epigastric tenderness on examination. The evaluation of patients with dyspepsia includes taking a comprehensive history and performing a physical examination. Although taking a patient history has its limitations in making an accurate diagnosis, it is useful in guiding the selection of subsequent diagnostic tests. Differential diagnoses of dyspepsia are best addressed using an anatomical approach. Patients with chronic dyspepsia lasting > 1 month should be evaluated for the presence of alarm features. Alarm features mandate an upper gastrointestinal endoscopy examination, as these may be suggestive of a malignancy. In patients without alarm features, a Helicobacter pylori test-and-treat strategy is cost-effective if the prevalence of H. pylori infection is high. Tests for H. pylori infection can be divided into non-invasive and minimally invasive tests. Many different antibiotic combination therapies (eg, triple therapy, quadruple therapy, levofloxacin-based therapy, sequential therapy, concomitant therapy, and probiotics with eradication therapy) are now available for the eradication of H. pylori infection. In patients who are symptomatic without an organic pathology, functional dyspepsia and other causes of abdominal pain need to be considered. Functional dyspepsia is best managed using a multifaceted approach by establishing a good physician-patient relationship, dietary and lifestyle interventions, medical therapy, psychotherapy, and the use of psychotropic medications. This review rationalizes the current-day recommendations for the evaluation and management of patients with dyspepsia in a clinical setting.