Our understanding of the underlying causes of asthma and, as a result, the treatment of asthma has advanced remarkably in the last decade. Still, the understanding of asthma and its control is not complete. In particular, a number of individuals with asthma either do not respond to standard asthma therapy or become unresponsive to therapy at some point in their treatment. Such individuals develop more severe asthma and are also at an increased risk for acute asthma attacks. Major goals of the Asthma Center research programs are to understand why some individuals have a limited response to standard therapy and why they progress to a more severe form of asthma. With that understanding we hope to identify new treatment approaches that will reduce the severity of asthma in these individuals.