Abstract Five decades of publications have been necessary to document the relationship between immune response and tissue injury in periodontitis. Multiple mechanisms have been implicated in the progression of tissue damage, including the controversial mechanisms of autoimmunity. The aim of this paper is the development of the theories that considered periodontal disease as an autoimmune entity with a historical narrative and descriptive view. Diverse theories have been referenced involving the innate and acquired immunity: generation of anti-neutrophil cytoplasmic antibodies (ANCA), Th17 cell function and IL-17, auto-antibodies to collagen and epithelial components of the periodontium, the role of NK cells T lymphocytes and T CD5, development of molecular mimicry, among others. In conclusion, it’s still difficult to classify periodontal disease as an stabilshed autoimmune disease, because its multifactorial nature makes it difficult to understand. However, the evidence is clear and comprehensive showing related autoimmune mechanisms, which could eventually explain the progression and its relation to systemic events such as cardiovascular disease and atherosclerosis.