In the past few decades, there has been an increase in demand for safety evaluation and control of dental materials used daily in dentistry; however, this task is difficult and cumbersome. Dental materials that are passive and do not react with the oral environment will be more stable and have superior durability. It is expected that dental materials will be universally accepted and will not cause harm or injury to the surrounding structures in the oral cavity. This is an entirely negative approach to the material tolerance and biocompatibility, and hides the possibility that some positive gains can be achieved. Side-effects of dental materials are believed to be rare, and generally, those that have been reported are mild. There are wide varieties of materials used in dentistry, which include liners, irrigants, intracanal filling materials, intracanal medicaments, prosthetic materials, restorative materials, subgingival implants, and mouth rinses. Therefore, in this study, the biocompatibility of various commonly-used clinical materials used in contemporary dentistry was discussed.