The immune system is a complex array of cells and molecules operating in an orchestrated manner in order to protect the host from pathogenic microorganisms and exogenous noxious agents within our environment. However, destruction of host tissue may occur if the immune response is inadequate due to intrinsic or extrinsic mechanisms in cell function, or if there is a hyper-responsiveness due to dysfunctional regulatory mechanisms. The pathogenesis of periodontal disease is clearly of an inflammatory origin and, as such, has a close association with the Immune System. Unraveling the intricate mechanism by which the host responds to pathogens colonizing the tooth will lead to more sensitive means to detect subtle changes in disease activity, and more effective and predictable therapeutic modalities. The figure below is a simplified model reminding us of the complex nature of periodontal disease.