Health is not a static condition. It is a dynamic state in which the living and functioning organism or tissue remains in balance with a constantly changing environment. This constant process of readjustment to maintain a functional integrity is known as \"homeostasis\". It is a well-known fact that bacteria constitute an important part of environment and all the external surfaces in nature including living tissues are covered by bacteria, the skin, the gut and oral mucosa are of no exceptions. The host responds to the attack of bacteria and its toxins at various levels. There are two main components of the host response to plaque following as natural or innate immunity or nonspecific immunity and acquired or specific immunity. This chapter covers the acquired or specific immunity, contents of innate immunity, gingival epithelium, gingival crevicular fluid, complement, inflammatory cell response, characteristics of inflammatory cells, immunological mechanisms, and immunology of periodontal disease.