The pathogenesis, diagnosis, and optimal therapy of gastroesophageal reflux disease continue to be intensely investigated. A focus is on hiatus hernia as a contributor to sphincter incompetence and poor clearance. Acid is the most important damaging constituent of gastric refluxate, but the importance of alkaline reflux and nonsteroidal drugs continues to be debated. Exciting reports confirm that the human esophagus secretes bicarbonate in significant quantity. Swallowed salivary bicarbonate remains an important factor in the restoration of a neutral esophageal pH. Animal experiments confirm the presence of paracellular barriers to diffusion, and intracellular mechanisms to buffer acid. Epidermal growth factors and their receptors are present in human esophageal biopsies. The methodology and clinical usefulness of ambulatory pH monitoring and manometry in adults and children continue to be debated. The need for long-term treatment of reflux disease is underlined by studies of natural history in adults, which indicate that symptoms rarely resolve spontaneously. Acid inhibition with omeprazole or high-dose H2-receptor antagonists is the most effective medical therapy, and appears to be safe during 5-year, continuous treatment. Nissen fundoplication had advantages over low-dose H2-receptor antagonists in one 2-year study, but the greater effectiveness of modern therapeutic regimens means that further comparisons are required. Economic modeling shows that omeprazole is the most cost-effective medical treatment.