The human mouth is one of the main routes of entry into the body for foreign microorganisms. During the usual course of daily living the host may be invaded by microbes possessing various harmful qualities, or the host may acquire breaks in its defenses, or may undergo operative procedures. In these conditions, the microorganisms find themselves in inadequately protected tissues because of break in local barrier. As tissues are injured and microbes increase, a variety of signals in the host brings about mobilization and local accumulation of protective factors and these are generally sufficient to contain the pathogens, prevent their dissemination, and allow healing to proceed promptly. The purpose of this review is to study both innate and immunologically-mediated defense systems in the human mouth and to review extensively the functions of these various defense mechanisms in protecting the host from colonization with microorganisms and cancerous cells with particular emphasis on the oral cavity and its immediate surroundings.