Drug-induced injury of the gastrointestinal (GI) tract is increasingly common but generally under-recognized. Although there is an overwhelming number of drugs that are associated with adverse GI effects, there is a limited number of characteristic injury patterns that should prompt consideration of drug-induced GI pathology. These include the following: erosions, ulcers, and strictures; crystal deposition; parietal cell changes; reactive gastropathy; pseudodysplastic changes; microscopic colitis; infectious or necrotizing enterocolitis; ischemic colitis; focal active colitis; and increased epithelial apoptosis. This article reviews morphological and pathophysiological features of some of the more common and pathologically recognizable drug-related injury patterns and provides a practical guide for the recognition and diagnosis of drug-induced pathology in the upper and lower GI tract.