Today, there are several modalities to treat gastroesophageal reflux disease (GERD) (medications, endoscopic therapies, surgery) and such therapies can be used either singly, or in tandem, or in combination with the others, aiming at "normalization" of the patient's GERD-related quality of life and, if possible, esophageal acid exposure. Several intermediate end points or clinically significant outcomes have not been reached by some therapeutic modalities and no single modality is or can be perfect. Statistically significant improvements in these intermediate end points have been shown in "some" but not all studies. Although healing of esophagitis can be accomplished with either medical or surgical therapy, there is inadequate data with endotherapies, because most patients treated with endotherapies have had prior trials of proton pump inhibitors (PPIs) and hence healed their esophagitis. Effective prevention of complications, such as esophageal adenocarcinoma, remains challenging for all modalities. Patients who have not normalized their GERD-related quality of life with once or twice daily PPI therapy should undergo functional esophageal evaluation with pH testing and esophageal motility study and they should be evaluated by both an endoscopist and a surgeon. The decision on how to proceed should be made on the basis of the criteria for endotherapy and surgery, availability of local endoscopic and surgical expertise and patients' preference. Such multimodality therapy model is in many ways similar to the long-term management of coronary artery disease where pharmacotherapy, angioplasty, and bypass surgery are frequently used in tandem or in combination. Multimodality therapy aiming at normalization of GERD-related quality of life is an option today, and should be available to all patients in need of therapy. The target population for GERD endotherapy currently consists of PPI-dependent GERD patients, who have a small (<2-cm-long) or no sliding hiatal hernia, and without severe esophagitis or Barrett esophagus. Thus far, only Stretta and the NDO plicator have been studied in sham-controlled trials. Registries of complications suggest that these techniques are relatively safe, but serious morbidity, including rare mortality have been reported (for a continuous update on complications related to endoscopic therapies see: http://www.fda.gov/cdrh/maude.html). All can be performed on an outpatient basis, under intravenous sedation and local pharyngeal anesthesia. Future comparative studies with predetermined clinically significant end points, validated outcome measures, prolonged follow-up, and complete complication registries will eventually determine the precise role of endoscopic procedures for the patients with GERD.