For children living in inner cities, asthma tends to be more frequent and severe. To characterize, understand, and treat children with asthma living in the inner city more effectively, the National Institute of Allergy and Infectious Diseases established an Inner-City Asthma Program in 1991. In addition, the revised National Asthma Education and Prevention Program Expert Panel 3 report was introduced with new concepts for asthma management that are now centered on asthma control. The purpose of this review is to highlight features of the National Institute of Allergy and Infectious Diseases Inner-City Asthma Consortium Asthma Control Evaluation study that enhance our knowledge regarding the application of the asthma guidelines and to provide a summary of lessons learned from that important study. We recognized that asthma symptoms and exacerbations are theoretically linked to underlying inflammation of airways but are not direct indicators of inflammation. Based on the observations from the Asthma Control Evaluation study, we were impressed that a systematic guidelines-based approach improved asthma control significantly over the course of the 1-year treatment period.