This article focuses on the global settings where biopsy is done, the practical issues of how to do it, and what might be the benefit. The section on biopsy tips is condensed to provide very practical guidelines and some new information for even the most seasoned of endoscopists. This article covers topics such as the three histologic zones of the stomach, when to biopsy to rule out neoplasia, and biopsy in benign gastric mucosal disease.