Studies performed in numerous laboratories over several decades have demonstrated the feasibility of immunizing experimental rodents or primates with protein antigens derived from Streptococcus mutans or Streptococcus sobrinus against oral colonization by mutans streptococci and the development of dental caries. Protection has been attributed to salivary IgA antibodies which can inhibit sucrose-independent or sucrose-dependent mechanisms of streptococcal accumulation on tooth surfaces according to the choice of vaccine antigen. Strategies of mucosal immunization have been developed to induce high levels of salivary antibodies that can persist for prolonged periods and to establish immune memory. Studies in humans show that salivary antibodies to mutans streptococci can be induced by similar approaches, and that passively applied antibodies can also suppress oral re-colonization by mutans streptococci. Progress towards practical vaccine development requires evaluation of candidate vaccines in clinical trials. Promising strategies of passive immunization also require further clinical evaluation. Copyright © 2004 S. Karger AG, Basel.