For children living in the inner city, asthma tends to be more frequent and severe. Although the causes for this heightened severity of asthma are not clearly established, environmental allergens likely play a major role. To characterize, understand, and treat children with asthma living in the inner city better, the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health established an Inner City Asthma Program in 1991. Over the past 15 years, 3 separate inner-city asthma research networks have been formed and funded by this institute. The work from these programs has led to important observations including evidence that environmental allergens, particularly cockroach, are important for sensitization and severity of asthma of the affected children. Furthermore, reductions in the allergen load can lead to improved asthma control. The most recent program, the Inner City Asthma Consortium, was formed in 2002 with a goal to develop immune-based therapy for children with asthma in the inner city and to determine mechanisms of these therapies as well as immunopathogenesis of asthma in these high-risk children. This article reviews these programs and how they have begun the effort to understand and treat children with asthma who live in inner cities better and what their findings mean in relationship to unique features of asthma in inner city children.