Pain and inflammation are common problems in clinical practice. Anti-inflammatory drugs are one of the most often prescribed groups of medications. The issue is that they carry gastrointestinal (GI) and cardiovascular (CV) risks. Therefore, anti-inflammatory drugs should be used mostly in the setting of inflammation. Non inflammatory pain can be managed with other groups of drugs and therapies. For patients who do need anti-inflammatory agents, the choice is dependent on the GI and CV risk profile of the patient. Where possible, efforts should be directed to the underlying cause of the pain and inflammation.