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Heartburn (pyrosis) can be defined as a burning sensation behind the sternum. Heartburn is typically caused by stomach acid that has refluxed back into the esophagus through the lower esophageal sphincter (which is normally closed except when swallowing). Most people who experience heartburn actually produce normal amounts of stomach acid, so heartburn is a problem of acid in the wrong place, not the production of too much acid. Lifestyle modifications that may reduce the risk of heartburn episodes include elevating the head of the bed by 6 to 8 inches, decreasing/avoiding certain foods (eg, chocolate, peppermint, fatty foods, caffeine, citrus, and tomatoes), avoiding large meals, and losing weight (decrease abdominal pressure). When lifestyle modifications are insufficient, there are numerous heartburn therapy options available over the counter. All 3 major categories of over-the-counter heartburn therapies are targeted at reducing acid already present in the esophagus (eg, antacids) or reducing gastric acid production (histamine2-receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]). Antacids can provide rapid-onset heartburn relief by neutralizing acid already present in the esophagus. However, the transient increase in stomach pH caused by the antacid stimulates acid production, rapidly returning the stomach to a low pH. This rapid return to a low pH is why antacids do not prevent subsequent heartburn episodes and why frequent dosing (eg, up to 15 antacid tablets per day) may be required. Histamine2-receptor antagonists competitively inhibit 1 of the 3 stimuli for gastric acid production, which can slow acid production, so even a single dose can have a moderate effect on gastric pH. With repeat dosing, however, H2RAs rapidly develop tolerance that results in decreased acid control. While H2RAs can be effective for treating an isolated heartburn episode, they are less effective for controlling acid with repeat dosing (eg, frequent heartburn, defined as ≥2 days per week). Furthermore, H2RAs have an analgesic effect in the esophagus that is independent of acid control, so the esophagus may remain exposed to acid, even though the heartburn has been relieved. In contrast, PPIs block acid production at the final step, the proton pump, regardless of the 3 stimuli causing acid production. Proton pump inhibitors do not develop tolerance, and acid control actually increases over the first several days of dosing to a peak/sustained effect beginning on dosing day 4. Thus, PPIs provide both superior acid control and superior treatment of frequent heartburn when compared with H2RAs. Proton pump inhibitors show a dose-responsive effect on heartburn with less than 20 mg/d, but there is no additional heartburn control with higher doses (>20 mg), so the optimal dose for treatment of frequent heartburn is 20 mg/d. Treating frequent heartburn with a minimal effective dose is consistent with the 2013 treatment guidelines established by the American College of Gastroenterology. If frequent heartburn is not effectively treated with 2 weeks of an over-the-counter therapy, then the patient should be evaluated by a physician. Furthermore, the presence of 1 or more alarm symptoms (eg, difficulty swallowing, painful swallowing, gastrointestinal bleeding, iron deficiency/anemia, weight loss, early satiety, and vomiting) should be evaluated by a specialist.