Purpose of Review Periodontal regenerative therapy aims to completely restore the tooth’s supporting tissues (e.g., periodontal ligament, root cementum, alveolar bone, and gingiva) which have been lost following periodontal disease or trauma. The histologic outcomes should translate in substantial clinical improvements evidenced by probing depth reduction, gain in clinical attachment level, and bone fill. The present review provides a brief overview of the current status of periodontal regenerative therapy. Recent Findings There is plenty of evidence to support the use of guided tissue regeneration (GTR) techniques and the application of enamel matrix proteins (EMD) onto the exposed root result in true periodontal regenerative. The use of various growth factors and autologous blood concentrates for periodontal regeneration also have produced positive results, but more studies are needed. In general, both GTR and EMD, alone or in combination with bone grafts or substitutes, result in larger clinical improvements compared to conventional periodontal treatment for deep intrabony and furcation Class II defects. Important factors that negatively impact on the clinical outcomes of periodontal regeneration procedures are smoking, large number of remaining sites with bleeding on probing, bad oral hygiene, and increased tooth mobility. Conclusions The magnitude of improvement arising from periodontal regenerative techniques and procedures depends largely on operator skills, not only in terms of dexterity but also on the ability to choose the best approach regarding the surgical technique and the regenerative technology depending on patient- and site-specific criteria. The clinical improvements after regenerative treatment can be preserved on a long-term basis on the majority of treated sites, provided that patients do not smoke, keep high oral hygiene standards, and attend regularly SPT.