Can infection with the dental caries pathogen, Streptococcus mutans, be intercepted or modified immunologically? Resolving this question requires answers to many questions: What are the pathways by which this cariogenic streptococcus enters and accumulates in the dental biofilm? Can bacterial components associated with virulence induce immune responses? What is the level of maturity of immune pathways in the oral cavity of the young child at the time of infection? Can immune strategies deal effectively with chronic S. mutans infections? Are these vaccines safe? Many such questions have been answered. For example, preclinical application of modern methods of mucosal vaccine design and delivery has routinely resulted in protection from dental caries caused by S. mutans infection, using antigens involved in the sucrose-independent or sucrose-dependent mechanisms of infection by these cariogenic streptococci. Passive administration of antibody to functional epitopes of S. mutans virulence antigens has also provided a degree of protection in preclinical studies and small-scale human investigations. The caries-protective capacity of active immunization with dental caries vaccines now awaits proof of principle in pediatric clinical trials.