The pathophysiology of peptic ulcer disease has yet to be completely elucidated. This article reviews in detail possible mechanisms involved in peptic ulcer development. Aggressive factors (acid and pepsin), defensive factors (mucus, bicarbonate secretion, blood flow, and cell junctions) and repair processes (growth factors and restitution) are discussed. Imbalances of these factors may be due to Helicobacter pylori, nonsteroidal anti-inflammatory drugs, stress, smoking, or intrinsic defects.