A growing body of research supports the role of outdoor air pollutants in acutely aggravating chronic diseases in children, and suggests that the pollutants may have a role in the development of these diseases. This article reviews the biologic basis of children's unique vulnerability to highly prevalent outdoor air pollutants, with a special focus on ozone, respirable particulate matter (PM 2.5 [<2.5 microm in diameter] and PM 10 [<10 microm in diameter]), lead, sulfur dioxide, carbon monoxide, and nitrogen oxides. We also summarize understanding regarding health effects and molecular mechanisms of action. Practitioners can significantly reduce morbidity in children and other vulnerable populations by advising families to minimize pollutant exposures to children with asthma, or at a broader level by educating policymakers about the need to act to reduce pollutant emissions. Management of children with asthma must expand beyond preventing exposures to agents that directly cause allergic reactions (and therefore can be diagnosed by means of skin tests) and must focus more attention on agents that cause a broad spectrum of nonspecific, generalized inflammation, such as air pollution.