Dental caries remains one of the most common infectious diseases of mankind. Cariogenic micro-organisms enter the dental biofilm early in life and can subsequently emerge, under favorable environmental conditions, to cause disease. In oral fluids, adaptive host defenses aroused by these infections are expressed in the saliva and gingival crevicular fluid. This review will focus on methods by which mucosal host defenses can be induced by immunization to interfere with dental caries caused by mutans streptococci. The natural history of mutans streptococcal colonization is described in the context of the ontogeny of mucosal immunity to these and other indigenous oral streptococci. Molecular targets for dental caries vaccines are explored for their effectiveness in intact protein and subunit (synthetic peptide, recombinant and conjugate) vaccines in pre-clinical studies. Recent progress in the development of mucosal adjuvants and viable and non-viable delivery systems for dental caries vaccines is described. Finally, the results of clinical trials are reviewed, followed by a discussion of the prospects and concerns of human application of the principles presented.