Otitis media is a multifactorial disease, a result of complex host-microbial interactions. Understanding the pathogenesis of chronic otitis media (COM) is crucial for improving therapies. Direct detection of aggregated adherent otopathogenic bacteria on middle ear mucosal biopsies from children with COM demonstrated that biofilms were consistent with an infectious etiology in spite of culture-negative clinical data. This seminar will provide an overview of how biofilms contribute to chronic infections like COM, including problems in diagnosing the infectious agent in the polymicrobial context of the upper airway, the challenges of treatment and new therapeutic approaches on the horizon.