Drug toxicity in the gastrointestinal tract is a common and serious medical problem; the number of drugs that can harm the gastrointestinal tract is impressive. The morbidity, mortality, and medical costs associated with drug toxicity, even when restricted to the gastrointestinal tract, are probably underestimated. Drug-induced gastrointestinal tract pathology is very diverse and can mimic many non-drug-related conditions. Drug toxicity, whether direct or indirect, can be restricted to a segment of the gastrointestinal tract or affect the entire gastrointestinal tract. The consequences of drug toxicity are also quite variable and can range from unimportant pathology (e.g. the relatively common and usually benign drug-induced diarrhea) at one end of the spectrum, to fatal gastrointestinal tract hemorrhage or perforation at the other end of the spectrum. Better awareness of the possibility of drug-induced gastrointestinal tract pathology, by both gastroenterologists and pathologists, and better communication between gastroenterologists, pathologists and other specialists will improve the recognition of drug-induced gastrointestinal tract pathology, and, ultimately, improve patient care. This Review focuses on the most common and well-described drug-related clinicopathologic conditions of the gastrointestinal tract. Much discussion is, therefore, dedicated to NSAIDs--the most commonly prescribed drugs and consequently the drugs most commonly associated with gastrointestinal tract toxicity.