The role of allergen exposure in the etiology of allergic sensitization and asthma is complex. Advice on strategies to avoid domestic allergens remains contentious because trials of interventions aimed to prevent asthma or reduce symptoms have often failed to demonstrate benefits. Asthma management guidelines differ widely in their recommendations, while Web-based information often claims benefits associated with products. In this rostrum we argue that although many factors have a role in both the etiology and the exacerbation of asthma, allergen exposure probably remains an important contributor to the manifestations of the disease. Currently, there is no evidence-based framework for effective domestic allergen avoidance interventions to reduce chronic aeroallergen exposure. The development of an effective approach to allergen avoidance requires a better understanding of (a) the physical nature of chronic aeroallergen exposure and methods for measuring and reducing this, (b) the interaction between allergen exposure and innate immune modulators at different disease stages, and (c) markers enabling the identification of individuals who would benefit from this. The strategic risk of overemphasizing other novel mechanisms and approaches to asthma management is that we will prematurely abandon and fail to improve an existing approach that could have a significant impact on the development, progression, and symptoms of the disease.