Book excerpt: Globally, severe asthma is defined by the WHO as either (A) untreated severe asthma; (B) difficult-to-treat severe asthma; and (C) treatment-resistant severe asthma. Untreated severe asthma is a political problem: the children do not have access to the basic tools for asthma management, and when this is corrected, asthma outcomes are transformed. The problem in difficult-to-treat severe asthma is not the airway disease, but co-morbidities and behavioral factors. This is the group in which there are most asthma deaths, underscoring that severe asthma cannot be solely defined by levels of prescribed therapy. Treatment-resistant severe asthma is rare and challenging, and the problem is the airway pathology. These children require new and innovative therapies.