Gastroesophageal reflux disease (GERD) is a common clinical problem. Circumstantial evidence continues to suggest that infection with Helicobacter pylori may protect some patients from developing GERD and its complications. An empirical trial of a proton-pump inhibitor may now be a reasonable alternative to endoscopy or 24-hour pH testing for the diagnosis of GERD. Long-term follow-up data covering more than over a decade indicate that proton-pump inhibitors are effective and safe agents for the treatment of GERD. Furthermore, a strategy of proton-pump inhibitors first may be the most cost-effective approach to GERD. It remains unclear why some patients with GERD develop Barrett's esophagus, whereas others do not. Recent studies demonstrate the importance of pulses of acid or bile in increasing cell proliferation and cyclooxygenase-2 expression in Barrett's epithelium cell cultures. Short-segment Barrett's esophagus is now clearly associated with an increased risk of dysplasia or cancer compared to intestinal metaplasia of the cardia, and the cancer risk in this condition is similar to that with long-segment Barrett's esophagus. However, the overall cancer risk in patients with Barrett's esophagus is lower than previously estimated, at approximately 0.5% annually. Ablation techniques continue to show promise, but are not yet ready for routine clinical use. Endoscopic mucosal resection is a new treatment option for selected patients with high-grade dysplasia or superficial esophageal adenocarcinoma.