In this revision article it was tried to focus on the role played by pepsinogen/pepsin since its discovery until its practical use. Pepsinogen determination as the gastric acid secretion has different basal or stimulated secretion levels in the peptic ulcer, gastritis, etc. The methods for pepsinogen determination are evaluated, verifying that, in spite of radioimmunoassay utilization another methods less sophisticated have been used successfully. The pepsinogen seric levels (PSL) after stimulation with Histalog, discriminate the patients suffering from duodenal ulcer from normal individuals, and they are higher among men than women. A parallelism is made between pepsinogen-I and II finding out pepsinogen-I higher level in smoking individuals. The pepsinogen-I is increased in the duodenal ulcer and II in the gastric ulcer and both of them bent to be characterized as a genetic marker for peptic ulcer. Finally, the main clinical applicability for PSL group I determination is the detection of atrophic gastritis considering its potential for gastric malignancy.