Otitis media (OM; inflammation of the middle ear) comprises a group of disorders that are among the most common disorders of childhood. OM is also heritable and has effects on fecundity. This means that OM is subject to evolution, yet the evolutionary forces that may determine susceptibility to OM have not been adequately explored. Here I analyze evolutionary forces that may determine susceptibility to middle ear inflammation. These forces include those affecting function of the middle ear, host immunity, or colonization by and pathogenicity of bacteria. I review existing evolutionary models of host-pathogen interaction and coevolution and apply these to better understand the complex evolutionary landscape of middle ear infection and inflammation in humans, including factors determining transition between stable evolutionary strategies for host and bacteria. This understanding is then applied to an analysis of OM in indigenous populations to devise a new theory for OM prevalence in Australian Aborigine, Native American, Inuit, and Maori populations. I suggest that high prevalence in such groups may have resulted from encounters of these previously isolated populations with European immigrants in the 15th and 16th centuries. This exposed them to new strains of bacteria to which their immune system had not evolved immunity, perturbing a previously stable host-pathogen coevolutionary state.