Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used in the treatment of rheumatic diseases to relieve pain and signs of inflammation. However, when treated for ankylosing spondylosis (AS), NSAIDS exert both symptomatic and structure-modifying effects, by slowing down the development of vertebral ankylosis. The effect of these drugs, which underlines the formation of syndesmophytes, may be associated with their anti-inflammatory activity and ability to suppress abnormal bone proliferation. There is convincing evidence to support the capacity of NSAIDs, when long and continuously used, to reduce the rates of X-ray progression of AS. So the continuous use of NSAIDs must be now considered to be a mandatory component of pharmacotherapy for this disease. Their use should be continued even after achieving a marked clinical improvement. At the same time, this situation requires that the development of adverse reactions as structural and functional diseases of the gastrointestinal tract and cardiovascular system be thoroughly controlled in this situation. The danger of these complications determines the need for a physician's attention, obligatory consideration of risk factors, and rational choice of the safest NSAIDs.