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An ideal endodontic sealer should have many properties such as excellent seal after setting, dimensional stability, slow setting time to ensure sufficient working time, insolubility to tissue fluids, adequate adhesion with canal walls and biocompatibility. Genotoxicity is one of the important factors that influence biocompatibility of an endodontic sealer. This literature review was conducted to survey the genotoxicity, bioactivity and clinical perspectives of calcium silicate based sealers. We searched PubMed using appropriate MeSH keywords. Also a hand search was conducted in the related journals. Sixty eight articles were assessed finally. Genotoxicity and acute inflammation were high in calcium silicate based sealers. Both resin-based and calcium silicate based sealers caused perceptible tooth discoloration. There were controversies regarding the fracture resistance, apical patency and retreatability of different …