Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, and a growing body of evidence suggests that they have adverse effects in the lower gastrointestinal (GI) tract in addition to the well-described toxicity in the upper GI tract. Among NSAID users who develop adverse GI effects, the proportion with lower GI events is as high as 40%. Most of the available evidence is taken from case-control studies and case reports; no large, randomized, placebo-controlled study has specifically set out to determine the magnitude of NSAID toxicity on the colon. However, the data suggest that NSAIDs cause a primary macroscopic colitis, collagenous colitis, an increased risk of complicated diverticular disease, and exacerbations of preexisting inflammatory bowel disease. Treatment depends on withdrawal of the causative drug.