Objective: To review the progress that has been made in developing effective vaccines against the major bacterial pathogens responsible for acute otitis media. Data Source: Review of the literature with the aid of the MEDLINE database using the search terms otitis media and otitis media and vaccine. Data Extraction: Data were collected from clinical trials and laboratory studies. Findings: The heptavalent pneumococcal conjugated vaccine, Prevnar, reduced the incidence of acute otitis media from all causes by 7% in one study and by 6% in another study. For culture-positive pneumococcal otitis media, the point estimate of efficacy was 66.7% in one study, and the reduction in incidence was 34% in another study. A Phase I clinical trial has been completed successfully for a conjugated vaccine against nontypeable Haemophilus influenzae (NTHi), which has high immunogenicity for mice and rabbits, induces complement- mediated bactericidal activity against NTHi in rabbits, and is protective against NTHi otitis media in chinchillas. A conjugated vaccine against Moraxella catarrhalis elicits strong immune responses in mice and rabbits and induces complement-mediated bactericidal activity in rabbits. Conclusion: The prevention of otitis media is likely to require multivalent pneumococcal, NTHi, and M. catarrhalis vaccines, and these vaccines likely can be developed within a decade.