Pertussis, commonly known as whooping cough, is a vaccine-preventable respiratory disease with rising incidence due to declining vaccination rates and waning immunity. The most severe disease course is seen in unvaccinated or incompletely vaccinated infants less than 2 months of age, accounting for the largest burden of hospitalization and death, but adolescents and adults play an important role in pertussis transmission and outbreaks. Prompt recognition and diagnosis remain critical for hospitalists in the management of pertussis disease and prevention.