A biofilm is a highly organized, multicellular network of bacteria encased in a matrix and found in close association with a surface. Substantial effort in understanding the biologic and biochemical nature of biofilms has resulted in evidence supporting their importance in otitis media (OM), both from the perspective how pathogens develop viable communities in the middle ear as well as how this structure impedes successful antibiotic therapy. This new understanding may explain the recurrent nature of OM, and the persistence of middle ear fluid after infection. This article looks closely at biofilms in OM and suggests that an improved understanding of the unique properties of bacteria resident within a biofilm and the proteins they express while part of this organized community has the potential to identify novel and perhaps biofilm-specific molecular targets for the design of vaccine candidates for the prevention of OM.