© 2015 by S. Karger AG. All rights reserved. Periodontitis is a chronic inflammatory disorder affecting nearly 50% of adults in the United States. If left untreated, it can lead to the destruction of both soft and mineralized tissues that constitute the periodontium. Clinical man- agement, including but not limited to flap debridement and/or curettage, as well as regenerative-based strate- gies with periodontal membranes associated or not with grafting materials, has been used with distinct levels of success. Unquestionably, no single implantable biomate- rial can consistently guide the coordinated growth and development of multiple tissue types, especially in very large periodontal defects. With the global aging popula- tion, it is extremely important to find novel biomaterials, particularly bioactive membranes and/or scaffolds, for guided tissue (GTR) and bone regeneration (GBR) to aid in the reestablishment of the health and function of dis- tinct periodontal tissues. This chapter offers an update on the evolution of biomaterials (i.e. membranes and bioac- tive scaffolds) as well as material-based strategies applied in periodontal regeneration. The authors start by provid- ing a brief summary of the histological characteristics and functions of the periodontium and its main pathological condition, namely periodontitis. Next, a review of com- mercially available GTR/GBR membranes is given, followed by a critical appraisal of the most recent advances in the development of bioactive materials that enhance the chance for clinical success of periodontal tissue re- generation.