There is a long history of the study of Bordetella species in animal hosts, built on the foundation of Koch’s postulates: experimentally inoculating animals with virulent bacteria to define various pathogenic outcomes. Inoculation of mice, rats, pigs, baboons, and humans simulate whooping cough with increasing accuracy, albeit with exponentially increasing costs and difficulties. While most of the basic processes of immune activation and pathogenesis are quite similar from rodents to primates, relative to other pathogen infection systems there are marked differences that are important to consider. While most of this work has involved B. pertussis, the closely related species B. bronchiseptica naturally, and highly efficiently, infects a variety of animals, allowing aspects of pathogenesis to be examined in the context of natural infections. More recently, the ongoing transmission of B. pertussis within highly vaccinated populations has increased interest in understanding the nature of the transmission process. Several innovative animal models have now been established that allow transmission of B. bronchiseptica among mice, rabbits, and pigs, and transmission of B. pertussis among baboons. Together, these animal model systems have taught us most of what we know of the nature of the complex interactions within an individual host, transmission between hosts, and the past and ongoing evolution of these species. Recent and ongoing improvements of the historical animal infection systems, and the generation of new experimental infection systems to study pathogenesis and transmission, are critical to advance our understanding and control of the resurgence of this highly infectious disease.