Proton pump inhibitors (PPIs) can ameliorate reflux symptoms and heal esophageal injury by rapid inhibition of acid secretion. PPIs are used as an initial treatment as well as for maintenance purposes. Eight weeks are necessary for complete healing of esophageal injury. After initial therapy, symptomatic recurrence rates are as high as 85% within one year. Therefore, to maintain a good quality of life, many patients need half or usual dose of a PPI for maintenance. There are three kinds of maintenance therapy including continuous, intermittent, and on-demand therapy. PPIs are very safe to use. Adverse events including headache, skin rashes, diarrhea, and weakness have a very low prevalence. Longstanding use of a PPI, however, may be associated with several medical problems such as community-acquired infection and osteoporosis because of a chronic intragastric hypochlorhydric state. PPIs are definitely superior to H2-receptor antagonists and other medications in terms of their treatment potency and safety.