Analgesics play an important role in the management of dental pain, primarily as adjuncts to definitive interventions. Traditionally, non-opioid/opioid combinations (acetaminophen with codeine or hydrocodone) have been the analgesics of choice for the routine management of pain in dentistry. Recently, however, a strong association between opioid prescribing and the current opioid crisis has been convincingly demonstrated, and it appears that reductions in legitimate opioid prescribing are linked to increases in heroin use. The rationale for using opioids for dental pain was not entirely evidence-based and included the perception that “controlled substances” should be more efficacious than nonaddictive agents. However, concerns over increasing abuse and diversion of opioids as well as increasingly strong scientific evidence for superior pain relief provided by nonsteroidal anti-inflammatory drugs (NSAIDs) have combined to fundamentally change the contemporary approach to the management of acute dental pain (Moore et al., Cochrane Database Syst Rev (9):CD008659, 2015). Following the approval of ibuprofen by the Food and Drug Administration in 1974, an ever-expanding array of drugs in the NSAID class, primarily for the management of osteoarthritis and musculoskeletal pain, requires careful evaluation of which agents are best-suited for use in dentistry. This chapter is focused on non-opioid oral analgesics for control of acute pain, with an emphasis on high-level scientific evidence. The management of chronic orofacial pain is beyond the scope of this chapter and will not be covered.