Dyspepsia is the medical term for difficult digestion. It consists of various symptoms in the upper abdomen, such as fullness, discomfort, early satiation, bloating, heartburn, belching, nausea, vomiting, or pain. The prevalence of dyspepsia in the western world is approximately 20% to 25%. Dyspepsia can be divided into 2 main categories: “organic” and “functional dyspepsia” (FD). Organic causes of dyspepsia are peptic ulcer, gastroesophageal reflux disease, gastric or esophageal cancer, pancreatic or biliary disorders, intolerance to food or drugs, and other infectious or systemic diseases. Pathophysiological mechanisms underlying FD are delayed gastric emptying, impaired gastric accommodation to a meal, hypersensitivity to gastric distension, altered duodenal sensitivity to lipids or acids, altered antroduodenojenunal motility and gastric electrical rhythm, unsuppressed postprandial phasic contractility in the proximal stomach, and autonomic nervous system-central nervous system dysregulation. Pathogenetic factors in FD are genetic predisposition, infection from Helicobacter pylori or other organisms, inflammation, and psychosocial factors. Diagnostic evaluation of dyspepsia includes upper gastrointestinal endoscopy, abdominal ultrasonography, gastric emptying testing (scintigraphy, breath test, ultrasonography, or magnetic resonance imaging), and gastric accommodation evaluation (magnetic resonance imaging, ultrasound, single-photon emission computed tomography, and barostat). Antroduodenal manometry can be used for the assessment of the myoelectrical activity of the stomach, whereas sensory function can be evaluated with the barostat, tensostat, and satiety test. Management of FD includes general measures, acid-suppressive drugs, eradication of H. pylori, prokinetic agents, fundus-relaxing drugs, antidepressants, and psychological interventions. This review presents an update on the diagnosis of patients presenting with dyspepsia, with an emphasis on the pathophysiological and pathogenetic mechanisms of FD and the differential diagnosis with organic causes of dyspepsia. The management of uninvestigated and FD, as well as the established and new pharmaceutical agents, is also discussed.