NSAIDs are the basic and most commonly used drugs with documented efficacy in the treatment of inflammatory and pain. Effect of NSAIDs is associated with the inhibition of cyclooxygenases. The reason of most of the adverse effects of NSAIDs is inhibition of COX- 1 and therapeutic effect depends on the inhibition of COX-2. Side effects of NSAIDs may occur more than half of patients and is particularly relevant in the gastrointestinal tract, followed by cardiovascular system or other organs. The most common symptoms are dyspeptic, but it can also lead to gastrointestinal bleeding or perforation, and it can even cause death of the patient. It has been shown that the lowest risk of bleeding from the upper gastrointestinal tract are present in the application of ibuprofen, nimesulide, diclofenac and dexketoprofen. Very important is individual to the patient’s choice correct form and method of administration of drug.