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Biologic medications (BMs) are increasingly used for the management of systemic chronic inflammatory diseases. These diseases are often associated with a higher prevalence of apical periodontitis (AP) and periodontitis (P). The purpose of this systematic review was to ascertain the interactions between AP and/or P and BMs. The review was registered in the PROSPERO database (CRD42017054756). Electronic searches were performed on Pubmed Medline, Scopus and The Web of Science from their inception through to 20 March 2018. The references of the articles selected were checked. The keywords were chosen based on a pilot search, which aimed to find the most frequently prescribed BMs. The included studies were appraised qualitatively using appropriate tools. Thirty-five articles met the inclusion criteria, comprising 16 non-randomized clinical studies, 12 in vivo animal studies and 7 case reports. Quality of information was assessed as high in 18 articles, moderate in 16 articles and low in 1 article. BMs in patients suffering from chronic inflammatory diseases seems to inhibit the progression of AP and P, and to enhance the healing response to periodontal and endodontic treatment. A healthier condition of the periodontal tissues seems to be associated with a better response of the patient to BMs therapy.Abbreviations and acronyms: AP = apical periodontitis; BM = biologic medications; P = periodontitis; RANKL = receptor activator of nuclear factor kappa-Β ligand (RANKL).