The prevalence of asthma has increased worldwide. The reasons for this rise remain unclear. Various studies have reported an association between acetaminophen, a widely used analgesic, and diagnosed asthma. In a prospective cohort study, the rate of newly diagnosed asthma was 63% higher among frequent acetaminophen users than nonusers in multivariate analyses. Studies of patients with asthma suggest that acetaminophen challenge can precipitate a decline in FEV1 > 15% among sensitive individuals. Plausible mechanisms to explain this association include depletion of pulmonary glutathione and oxidative stress. This article reviews the existing literature and evaluates the epidemiologic and pathophysiologic evidence underlying a possible link between acetaminophen and asthma.