Periodontal diseases are initiated by Gram-negative tooth associated microbial biofilms that elicit a host response, with resultant osseous and soft tissue destruction. In response to endotoxins derived from periodontal pathogens, several osteoclast- related mediators target the destruction of alveolar bone and supporting connective tissues. Major drivers of this aggressive tissue destruction are matrix metalloproteinases (MMPs), cathepsins,cytokines and other osteoclast-derived enzymes. This book focuses on the downstream factors of the osteoclast responsible for the degradation of bone and soft tissues around teeth. Furthermore various therapeutic approaches that target MMPs, cytokines,cathepsins and other osteoclast-derived enzymes , such as MMP inhibitors, chemically modified tetracyclines, subantimicrobial formulations of tetracycline analogues, and various new agents such as periodontal vaccines, Probiotics, Grape seed proanthocyanidins, Cranberry fraction, omega 3 fatty acid, locally administered HMT agents are discussed. In addition, studies using other agents for the preservation of bone mass, such as bisphosphonates that inhibit osteoclast recruitment, are highlighted.