Although asthma affects nearly 8% of the adult population, most of these patients have mild-to-moderate disease that can be controlled with appropriate treatment. It is estimated, however, that 5% to 10% of patients with asthma have severe disease that is unresponsive to typical therapeutics, including corticosteroids. Because patients with severe asthma are disproportionately affected by their disease, in terms of both impaired lifestyle and health care costs, the National Heart, Lung, and Blood Institute sponsored a workshop on the pathogenesis of severe asthma. The goals of this workshop were to begin to define the characteristics of severe asthma. In these discussions, it was clear that many characteristics need to be considered in defining this phenotype of asthma, including symptoms, intensity of therapy (including administration of systemic corticosteroids), and impairment of lung function. Also discussed were potential mechanisms of severe asthma including the role of allergic diseases, which may play less of a role in severe asthma than in mild-to-moderate disease, and infections. A major limitation to control of severe asthma is the recalcitrant response of these patients to usual therapy including systemic corticosteroids; the potential of other therapies was reviewed. From these discussions, recommendations were made for future research needs to gain insights into a difficult therapeutic and possibly novel mechanistic area of asthma.