A number of methods have evolved through the years in probing the dysfunction that impacts mechanics and ventilation in asthma. What has been consistently found is the notion of heterogeneity that is not only captured in the frequency dependence of lung mechanics measurements but also rendered on imaging as patchy diffuse areas of ventilation defects. The degree of heterogeneity has been linked to airway hyperresponsiveness, a hallmark feature of asthma. How these heterogeneous constriction patterns lead to functional impairment in asthma have only been recently explored using computational airway tree models. By synthesizing measurements of lung mechanics and advances in imaging, computational airway tree models serve as a powerful engine to accelerate our understanding of the physiologic changes that occur in asthma. This review will be focused on the current state of investigational work on the role of heterogeneity in asthma, specifically exploring the structural and functional relationships.