The first marketing authorization for nimesulide was approved in Italy in 1985. After one quarter of a century we evaluate its peculiar characteristics compared with other NSAIDs. Nimesulide is the only NSAID related to the arylsulfonamide class and is a "COX-2 preferential NSAIDs", because despite having a prevalent effect on COX-2, has a balanced action on both cyclooxygenase. The gastrointestinal absorption is rapid and complete and explains the short onset of action. Nimesulide is rapidly distributed in the synovial fluid, where it persists longer than in the blood, thus contributing to effectiveness of the drug in pain control. From the standpoint of safety, nimesulide arises NSAIDs with lower risk of upper gastrointestinal bleeding thanks to its preferential activity on COX-2. In relation to the risk of severe hepatic reactions, the benefit/risk profile of nimesulide was considered by european regulatory authorities similar to other NSAIDs. Respecting international guidelines, the use of nimesulide in pain management, as that of other NSAIDs, must be considered as an alternative therapy when paracetamol is ineffective, or where the pain is caused or supported by an inflammatory process.