Controversies exist in clinical and pharmacologic aspects of endodontics. For example, a recent study raised doubts about the benefits of incision and drainage for patients with fluctuant swellings of endodontic origin. However, incision and drainage has historically been the standard treatment for that condition. An assessment of the research and its significance for clinicians will be discussed. The appropriate use of opioids in dentistry continues to be a critical issue. In the face of an opioid epidemic, dentists have turned to over-the-counter analgesics. However, acetaminophen, ibuprofen and other NsAIDs have been associated with serious side reactions that are of concern especially when used by pregnant patients. These medications have been linked to childhood asthma/wheezing, behavioral problems, hyperkinetic activity and the incidence of myocardial infarcts. Another controversy concerning NsAIDS and acetaminophen is their value in pre meditating patients with irreversible pulpitis prior to inferior alveolar nerve blocks. The clinical implications of these controversies will be discussed.