The concept of vaccination against dental caries has existed almost the time that this disease was recognized to result from the colonization of teeth by acidogenic bacteria. An ideal dental caries vaccine must have broad coverage for all common cariogenic S. mutans strains and could be given by various routes and still be effective. The principle of vaccination against dental caries involves targeting various S. Mutans target antigens, such as adhesions, GTFs, and glucan binding proteins. These substances are used for vaccine preparation. Most of the recent experimental efforts have been directed toward these compounds. This chapter describes the basic concepts of the molecular pathogenesis of dental caries, basic concepts of immunity and mechanism of action of dental caries vaccine, along with the routes for dental caries vaccination and the delivery systems. Also highlighted, from the public health viewpoint are the timing and target population for caries vaccination, recent advances, its prospects and public health aspects. This chapter, thus, serves as a rich source of information on dental caries vaccine for both dental undergraduate and postgraduate students.