This chapter discusses pathophysiology of peptic ulcer, which is a disorder resulting from autodigestion of the gastric or duodenal mucosa by gastric juice. Mucus seems to act as a barrier to both enzymes and acid. Mucus production is subject to regulation by neurohumoralfactors. Secretion of gastric mucus is stimulated by vagal stimulation as well as by secretion, which ensures adequate protection right from the beginning of a meal till neutralization of acid in the small intestine. Bicarbonate ions help in reducing the amount of acid which reaches the gastric mucosa. Prolonged emotional tension led to sustained hyperfunction of the stomach. Recurrence of peptic ulcer is often seen during periods of long-standing emotional stress suggesting that psychological factors may be involved in its causation. Such diseases where mental stress manifests as a physical illness are known as psychosomatic diseases. Gastric ulcer is often associated with normal or diminished acid secretion.