After third molar extractions, one of the most reported complications is postoperative pain. Various antipyretic analgesics are used to reduce an inflammation and to relieve a pain after the extraction. One of the most prescribed regimens is a combination of acetaminophen and hydrocodone, such as Vicodin. Another popular regimen is acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs). In addition to these regimens, some providers also prescribe postoperative corticosteroids to reduce postoperative inflammation and pain. Other than the NSAIDs, various antipyretic analgesics are used, including acetaminophen (paracetamol), a non-pyrine analgesic, and an opioid analgesic such as tramadol. It is important to understand the properties of these drugs and chose appropriate one (Table 14.1) (Baker and Perazella 2020; Becker 2010). This chapter will briefly go over the mechanisms of action of these popular postoperative regimens and the reasonings for each regimen to manage postoperative pain after third molar extractions.