Patient pain is a common problem faced by dentists and oral and maxillofacial surgeons. Craniofacial pain may be caused not only by inflammation in the teeth, but also various oral, facial, and nerve-related diseases, as well as tumors. Non-steroidal anti-inflammatory drugs (NSAIDs) constitute the basis of the analgesic ladder. According to the World Health Organisation (WHO), NSAIDs are the first-line drugs in relieving pain and inflammation of oral conditions. NSAIDs have been used in almost every field of dentistry. These drugs are applied in conservative dentistry and endodontics, dental surgery, orthodontics, periodontology, and oral mucosal diseases, as well as head and neck oncology. Some of the NSAIDs exhibit additional therapeutic effects, such as inhibition of nuclear factor kappa B (NF-kappaB) and inducible nitric oxide synthase (iNOS), and reduction of oxidative stress or leukocyte passage to the site of inflammation, which further reduces inflammation in tissues. The topical use of NSAIDs in dentistry is worthy of attention and further research as it will significantly reduce the adverse effects of systemic administration. This article aims to review the preclinical and clinical studies that have supported the role of NSAIDs in dentistry.