Drug‐induced mucosal injury (DIMI) in the gastrointestinal tract is important to recognise, partly because cessation of the culprit agent alone may result in resolution of symptoms. An ever‐growing list of medications, including newer immunotherapeutic agents and targeted therapies, can cause gastrointestinal inflammation of varying severity. However, the diagnosis of DIMI is challenging, as a single drug can induce a variety of histopathological patterns of injury including acute colitis, chronic colitis, microscopic colitis, apoptotic colopathy, and ischaemic‐type colitis. An additional consideration is the potential clinical, endoscopic and histological overlap of DIMI with gastrointestinal mucosal injury secondary to other entities such as inflammatory bowel disease (IBD). We discuss DIMI of the gastrointestinal tract with an emphasis on histological patterns that mimic IBD, histological features which may distinguish the two entities, and the diagnostic role and limitations of the pathologist.