Severe asthma affects only a small percentage of the asthma population. However, these patients remain poorly understood and difficult to treat. Because the numbers are relatively small (10% or less of the asthma population), a network approach with shared protocols, samples, and data provides a unique opportunity to recruit the numbers of subjects necessary to perform adequately powered studies. The Severe Asthma Network (Severe Asthma Research Program) was established by the National Heart, Lung, and Blood Institute in 2001 to advance collectively the study of severe asthma to determine factors that differentiated these patients or subjects from those with milder asthma. Nearly 800 subjects have been recruited in less than 4 years to begin to address these differences. Future studies will specifically evaluate the role of inflammatory/oxidative processes, infection, genetics, and the distal lung in the pathogenesis of severe asthma.