Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) effects in Ankylosing Spondylitis (AS) are only suspensive but because of their rapid efficacy on inflammatory symptoms they are the first-line treatment in AS. Short term efficacy of NSAIDs in AS is observed for most patients but the correlation of NSAID intake with the long term prognosis and its potential influence on the structural progression of the disease is still unknown. Therefore, and due to the gastrointestinal side effects of these drugs, daily practice is mostly in favour of discontinuous intake of NSAIDs, following the clinical relapses. However, the recent introduction of specific Cox-2 inhibitors, with a lower risk of severe gastrointestinal adverse events, may modify this attitude. Moreover, some patients are inadequately relieved of pain and inflammation by NSAIDs. The number of NSAIDs to be tested and for each NSAID, the optimal dosage that must be used before categorizing a patient as "refractory to NSAID therapy" have to be clarified. The recent determination of response and remission criteria for NSAIDs therapy is the first step towards well-defined guidelines for short-term and long-term management of NSAIDs in AS.