Prokinetic drugs theoretically have the ability to correct the pathophysiologic abnormalities of gastrointestinal motility that lead to gastroesophageal reflux disease. However, the prokinetic agents bethanechol and metoclopramide have been associated with central nervous system and other side effects, as well as uncertain efficacy. In addition, erythromycin seems unsuitable for use as an oral prokinetic agent. A recently introduced prokinetic agent, cisapride, has a minimum incidence of side effects and is effective in the treatment of reflux symptoms, but trials in the United States have not confirmed the symptomatic improvement or healing of erosive esophagitis that has been demonstrated in studies abroad. An expanded role may unfold for cisapride and additional new prokinetic drugs as primary therapy for reflux in some patients, as adjunctive treatment with an antisecretory agent, or as maintenance treatment for a subset of patients with gastroesophageal reflux. Therapy tailored to individual pathophysiology is appropriate and may offer cost savings and improved clinical outcome.