Heterogeneity is an intrinsic property of the lungs. Structurally, it is evident in the complex branching of the airways and the spatial distribution of tissue throughout the lung. Functionally, this translates to variation in the distribution of airway resistance and lung compliance, resulting in disparity in the filling and emptying rates between individual compartments, and consequently heterogeneous distribution of ventilation. Disease causes pathological alterations to structure and function, causing corresponding changes to heterogeneity, which can be measured via functional imaging, oscillometry or gas washout methods. This review describes key relevant concepts, and presents the most recent evidence for the significance of heterogeneity as a marker of disease severity and potential predictor of treatment or intervention response.