Biologic agents are targeted immune modulating agents that have been widely used in the treatment of inflammatory and neoplastic conditions with favorable results. The purpose of this review is to provide an update on the biologic agents that have been used in the treatment of diseases that affect the oral mucosa. Identification of relevant data, case reports and case series was performed using the PubMed-MEDLINE database and electronic databases of accredited organizations such as the European Medical Agency, US Food and Drug Administration, and clinicaltrials.gov (USA). According to the literature, the use of biologic agents in patients with oral diseases is limited mainly to patients suffering from refractory forms of immune-mediated diseases of the oral cavity. Biologic agents were used in all cases as off-label indications. Patient's response varied, but in general biologic agents could be considered as a therapeutic option in patients with no other alternative. A point requiring extra precaution is their safety profile because severe life threatening infections are among their side effects. Another aspect that limits their broader use is their high economic cost. We aimed to provide a practical update for the clinicians who deal with oral diseases, covering as many aspects as possible of the applications of biologic agents in oral diseases reported to date.