In the past, various models including the autoimmunity model have been proposed to explain the pathogenesis of periodontal diseases. The aimof this reviewis to introduce the pathogenic role of anti-neutrophil cytoplasmic autoantibodies (ANCAs) in various autoimmune diseases and compare these conditions with periodontal disease to elucidate common pathogenicmechanisms.Also,anovelmodel toexplain thepathogenesis of periodontal disease basedontheconcept ofANCAassociated autoimmunity is proposed. This encompasses a wide array of biochemical mediators that range from direct and indirect initiators of ANCA production and eventual release of proinflammatory mediators and free radicals, all of which have been implicated in periodontal tissue destruction in the past. In addition, specific links between the typical ANCA-associated diseases and periodontal disease are discussed. Finally, a new paradigm in the periodontal diseaseassociated destruction is proposed that includes the currently accepted mechanism, namely, the genetic-microbial-host interactions. J Periodontol 2006;77:1304-1313.