The prevalence and incidence of adverse drug interactions involving NSAIDs remain unknown. To identify those proposed drug interactions of greatest clinical significance, it is appropriate to focus on interactions between commonly used and/or commonly coprescribed drugs, interactions for which there are numerous well documented case reports in reputable journals, interactions validated by well designed in vivo human studies and interactions affecting high-risk drugs and/or high-risk patients. While most interactions between NSAIDs and other drugs are pharmacokinetic, NSAID-related pharmacodynamic interactions may be considerably more important in the clinical context. However, prescriber ignorance is likely to be a major determinant of many adverse drug interactions. Adverse drug interactions involving NSAIDs may be restricted by rational prescribing and by careful monitoring, particularly high-risk patients, drugs and therapy periods. Prescribing NSAIDs is relatively contra-indicative for patients on oral anticoagulants due to hemorrhage and for patients taking high dose methotrexate due to bone marrow toxicity, renal failure and hepatic dysfunction. Combination NSAID therapy cannot be justified since toxicity may be increased without any improvement in efficacy. Where lithium or antihypertensives are coprescribed with NSAIDs, aspirin or sulindac are preferred and close monitoring is mandatory for lithium toxicity and hypertension respectively. Phenytoin or oral hypoglycemic agents may be administered with NSAIDs other than pyrazoles and salicylates, provided, the patients are monitored carefully at the initiation and cessation of NSAID treatment. Digoxin, aminoglycosides and probenecid may be coprescribed with NSAIDs but close monitoring is required, particularly for high-risk patients such as the elderly. Indomethacin and triamterine should be avoided due to the risk of renal failure, high dose aspirin should be replaced by naproxen in patients on sodium valproate and care is required when corticosteroids are administered to patients taking salicylates long term in high dosage. Interactions between NSAIDs and antacids or cholestyramine are generally avoidable by administering these drugs at different times.