In asthma, diffuse and homogeneously distributed airway abnormalities have been thought responsible for symptoms and disease worsening, despite evidence over six-decades ago of ventilation heterogeneity using multiple-breath gas-washout studies. Such ventilation heterogeneity could stem from heterogeneously distributed airway abnormalities and, recently, pulmonary imaging including nuclear medicine methods, x-ray computed tomography (CT) and magnetic resonance imaging (MRI), has revealed focal ventilation defects and abnormal, heterogeneous ventilation patterns in asthmatics. In this review, we summarize pulmonary functional MRI findings that provide supportive evidence that in asthmatics, some ventilation abnormalities are temporally and spatially persistent while others come and go intermittently, but in the same, predictable spatial locations. Importantly, MRI ventilation defects also worsen in response to methacholine and exercise in the same spatial locations, despite differing underlying asthma response mechanisms, and in most patients, ventilation defects improve post-bronchodilator. In asthmatics, focal ventilation defects have been shown to be quantitatively and spatially related to airways with abnormal wall and lumen morphology, possibly stemming from remodelling, smooth muscle dysfunction and/or inflammation that may occur concurrently or independently. Finally, because MRI ventilation defects were also shown to be related to eosinophilic airway inflammation, asthma symptoms and disease control, we think MRI may be considered clinically to guide asthma therapy decisions in patients, to develop novel therapies and better understand mechanisms of asthma progression and therapy response in individual patients.