The purpose of a root-end filling is to establish a seal between the root canal space and the periradicular tissues. As root-end filling materials come into contact with periradicular tissues, knowledge of the tissue response is crucial. Almost every available dental restorative material has been suggested as the root-end material of choice at a certain point in the past. This literature review on root-end filling materials will evaluate and comparatively analyse the biocompatibility and tissue response to these products, with primary focus on newly introduced materials.