The accomplishment of developing a truly adhesive bond between a restorative material and the natural tooth structures is the goal of adhesive dentistry. Dentine adhesive systems come into close contact with dental and oral tissue, especially the pulp and gingival cells. Due to this close and long-term contact, adhesives should exhibit a high degree of biocompatibility. Biocompatibility is one of the most important properties of dental materials, and adhesives are no exception. It has been long demonstrated that different components of adhesives can be released. Numerous in vitro investigations have shown that released monomers and other components can cause damage to cultured cells. In addition, many in vivo studies have shown that uncured components which reach the pulpal space cause inflammatory response and tissue disorganization. Only a combination of various in vitro and in vivo tests can provide an overview of the interaction of biomaterials with the host. Therefore, it is necessary on a regular basis to carry out and re-verify the biological compatibility of the increasing number of new dental materials. Adhesives should be biofunctional, protective, and preventive, with health-promoting effects that contribute to a better prognosis for restorative treatments and its biocompatibility.