Pertussis, or whooping cough, has had a dramatic resurgence in the past several years and is the most common vaccine-preventable disease in the world. The year 2012 marked the most cases in the United States in > 50 years. Large outbreaks have occurred in multiple states, and infant deaths have drawn the attention of not only health-care providers but also the media. Although the disease is theoretically preventable by vaccination, it remains a challenge to control. New vaccination strategies have been implemented across different age groups and populations of patients, but vaccine coverage remains dismally low. Acellular vaccines, although safe, do not afford the same long-lasting immunity as the previously used whole-cell vaccine. Ultimately, improvements in the development of vaccines and in vaccination coverage will be essential to decrease the burden of pertussis on society. This article provides a review of pertussis infection and discusses advances related to the epidemiology, diagnosis, treatment, and prevention of infection, as well as continued areas of uncertainty.