Otitis media is one of the most common childhood infections leading to doctor's visits and a leading cause of antibiotic prescriptions in children. Twin and family studies have confirmed that the predisposition of developing a bacterial middle ear infection is genetically determined. Several case-control studies have been performed to analyze genes involved in inflammatory processes in search of potential associations. Modern genome-wide association approaches that require no prior assumptions of the involvement of a given gene locus in the risk of otitis media are currently being used to identify otitis media genes, and will hopefully give more detailed information on the pathogenesis of childhood otitis media. That information could be used in finding the high-risk patient, in the prevention of the disease, and in the design of new treatments.