Nonulcer dyspepsia refers to epigastric discomfort/pain, gas, nausea, and disturbed digestion in patients without evidence of peptic ulcer disease or other pathology on diagnostic studies. Many patients have tried self medication with antacids or OTC H2 receptor antagonists with little or no success before presenting for evaluation. Although the current thinking is that treatment for concomitant Helicobacter pylori infection may not have an effect on symptom control, many physicians choose to treat with an appropriate combination of antibiotics and a proton pump inhibitor due to the relationship of gastric malignancies with H. pylori infections. Potential therapies include antacids, H2 receptor antagonists, proton pump inhibitors, and prokinetic agents. The prokinetic agents should be used for patients with dysmotility sympoms such as vomiting, bloating, or distension. If patients have a family history of GI malignancies or display any warning symptoms such as weight loss, anemia, guiac-positive stools, jaundice, dysphagia or odynophagia, then a more aggressive work up to include esophagoduodenoscopy, barium small bowel follow through radiography, and abdominal ultrasonography should be instituted. Other etiologies to consider include an atypical manifestation of cardiac ischemia, biliary colic, pancreatitis, carbohydrate malabsorption, Crohn’s disease, infections (giardiasis or strongyloidiasis), infiltrative diseases, ischemic bowel, collagen vascular disorders (systemic lupus erythematosus, scleroderma), drug side effect, gastroparesis, or malignancies of the GI tract or abdominal viscera.