Causes of the progression of periodontitis such as an imbalance between the immune response by the host by the release of inflammatory mediators in the response of the oral pathogenic dysbiotic biofilm have been identified. New insights on specific cell signaling pathways that appear during periodontitis have attracted the attention of researchers in the study of new personalised approaches for the treatment of periodontitis. The gold standard of non-surgical therapy of periodontitis involves the removal of supra and subgingival biofilm through professional scaling and root planing (SRP) and oral hygiene instructions. In order to improve periodontal clinical outcomes and overcome the limitations of traditional SRP, additional adjuvants have been developed in recent decades, including local or systemic antibiotics, antiseptics, probiotics, anti-inflammatory and anti-resorptive drugs and host modulation therapies. This review is aimed to update the current and recent evolution of therapies of management of periodontitis based on the adjunctive and target therapies. Moreover, we discuss the advances in host modulation of periodontitis and the impact of targeting epigenetic mechanisms approaches for a personalised therapeutic success in the management of periodontitis. In conclusion, the future goal in periodontology will be to combine and personalise the periodontal treatments to the colonising microbial profile and to the specific response of the individual patient.