The aim of this chapter is to increase the awareness of health-care professionals concerning potential adverse efects and drug interactions of non-steroidal anti-inlammatory drugs (NSAIDs), which are among the most widely prescribed medicines, globally. They have a variety of clinical applications due to their anti-inlammatory, analgesic, antipyretic, or antithrombotic efect, but these drugs are not entirely innocuous, since they could increase the risk of gastrointestinal and cardiovascular complications. Furthermore, the drugs from this class have the potential of altering the pharmacokinetics of associated drugs, and also pharmacodynamic interactions have been reported. The clinical signiicance, mechanisms, and epidemiology of the adverse efects and drug interactions of NSAIDs are presented in this chapter. Prevention strategies for particularly high-risk groups of patients are also exposed. Detailed and up-to-date information regarding the adverse efects and drug interactions of NSAIDs are needed for all healthcare professionals in order to maximize eicacy in treating various illnesses while minimizing the risks for the patients.