There is compelling evidence that many infectious diseases of humans are caused by more than one microorganism. Multiple diverse in vitro systems have been used to study these complex diseases, and although the data generated have contributed greatly to our understanding of diseases of mixed microbial etiology, having rigorous, reproducible and relevant animal models of human diseases are essential for the development of novel methods to treat or prevent them. All animal models have inherent limitations; however, they also have important advantages over in vitro methods, including the presence of organized organ systems and an intact immune system, which promote our ability to characterize the pathogenesis of, and the immune response to, sequential or coinfecting microorganisms. For the highly prevalent pediatric disease otitis media, or middle-ear infection, the chinchilla (Chinchilla lanigera) has served as a gold-standard rodent host system in which to study this multifactorial and polymicrobial disease.