Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with serious and sometimes fatal side effects as gastrointestinal ulcers, bleeding and less frequently kidney and liver damage. These side effects are caused primarily by the reduction of prostaglandin synthesis, which in turn deprives the stomach's self-protection mechanism. NSAIDs prevent prostaglandin formation by inhibiting the enzyme cyclooxygenase. Recent research has shown that there are two types of cyclooxygenase, one that produces the form of prostaglandin involved in the gastric protection and the other that produces the form of prostaglandin involved in inflammation. Current NSAIDs inhibit both forms of cyclooxygenase. Gastrointestinal lesions associated with NSAIDs are predominantly observed in the stomach and are defined under the term of "NSAID gastropathy". Intestinal lesions secondary to the ingestion of NSAIDs were only recently described. Rectocolic lesions induced by NSAID are frequent and severe. The noxious effect of NSAID on preexisting low pathologies can be differentiated from "de novo" induced acute and chronic lesions.