Biological agents (BA) are increasingly used effectively in the treatment of a range of disorders, but to date, their application in diseases affecting the orofacial region has been fairly limited. Several orofacial adverse effects related to BA have been recently reported. However, the evidence for such adverse reactions is not always strong, and some of the adverse effects of BA have only been reported in case reports or case series. Most reactions to BA reported thus far have been in association with antitumor necrosis factor-α agents, which is not surprising, as these are the most widely-used BA. In the present study, the orofacial adverse effects are reported with various BA in order to sensitize clinicians to the possibilities. In addition, we briefly summarize the mode of action and indications of these BA. As the use and range of BA increases, the number and diversity of adverse effects might well increase. Despite the adverse effects of biological agents, these may often be less serious than the adverse effects of the more traditional immunosuppressive agents.