Magnetic Resonance Imaging using hyperpolarized helium and xenon gas (HP gas MRI) is uniquely sensitive to aspects of lung function integral to that organ’s ability to sustain life. The mixing of freshly hyperpolarized inspired gas with gas already present in the lung can be directly assessed using HP gas MRI—by visualizing not just the inhalation of the contrast agent, but also its diffusion throughout the acinar structure and, in the case of xenon, its dissolution into tissue, binding to hemoglobin, and distribution to other organs via the circulatory system. In this way, the dynamics of HP gas in the lungs mirrors that of oxygen and carbon dioxide. Identifying barriers to gas exchange is central to understanding which aspects of a diseased lung are most tied to morbidity, and whether available treatments can resolve those deficits. While regional lung function abnormalities can be masked by clinical global metrics, HP gas imaging is capable of addressing the spatial scale of these inhomogeneities for regional minute ventilation, residual volume, local exchange with lung parenchyma tissues, and with that of red blood cells, all at a satisfactory resolution. This dissertation presents ‘multibreath’ approaches that involve imaging over a series of breaths—in which a single, rapid image is acquired during a short breath-hold at the same phase of the breathing cycle on each breath (end-inhale or end-exhale). Different image contrasts may be encoded to highlight various features (e.g., diffusion, gas exchange, etc.), but the overall goal is to assemble all of the images to better capture the complex dynamics of gas delivery in the functionally compromised lung during the relatively normalized—i.e., tidal—breathing that better reflects the limitations encountered in subjects’ daily life. This approach can distinguish abnormally slow-filling regions that may require several breaths to resolve, perhaps through partially blocked airways or collateral pathways, from those that are entirely nonfunctional. This distinction is important, as slow-filling parenchyma can comprise more than half of the lung volume in cases of severe disease, and must therefore be responsible for significant life-preserving gas exchange. Our multibreath approach for imaging lung ventilation and gas exchange is applied here to the diagnosis, classification, and monitoring of treatment response in chronic obstructive pulmonary disease (COPD). COPD encompasses several pulmonary disorders, including chronic bronchitis and emphysema, and is characterized by both altered lung structure and function. The obstruction associated with COPD is likely, at least to some extent, a disruption of balanced forces maintaining airway patency in the healthy lung. However, the root causes of structural and functional changes may differ among the various presentations of the disease. Because COPD is a complex disorder with multifaceted manifestations, it is an ideal disease model on which to test the efficacy of the functional imaging tools developed in this dissertation for both early diagnosis as well as monitoring both disease progression and treatment response. We propose that, in both diagnosing and assessing the response to an intervention, probing the deviation of functional inhomogeneities from that of healthy nonuniformity can reduce clinical uncertainty for each patient as well as elucidate treatment changes such that these effects can be emphasized in future therapeutic advances. We further believe that observing longer term alterations leading to loss of functional benefit can help to select patients and procedures yielding persistent quality of life gains. After establishing the multibreath imaging methodology and testing its short- and long-term reproducibility, the sensitivity of the imaging markers for detecting difficult-to-assess smoking-induced subclinical changes in asymptomatic smokers is evaluated and compared with that of current clinical pulmonary assessments. Next, the effectiveness of imaging-based markers in predicting future lung function decline in smokers was compared to current clinical diagnostic techniques. We then imaged COPD patients who underwent an expensive regional treatment, endobronchial valve placement, with the aim of localizing and quantifying the most probable contributors to both functional and subjective benefit. Finally, the last chapter presents a novel ‘dynamic’ imaging approach in which subjects are imaged continuously during five minutes of spontaneous tidal breathing to generate maps of lung function capable of elucidating transient gas flow defects, pulmonary vascular response to the heartbeat, and the lung’s contribution to systemic bloodflow—aspects of lung physiology and pathophysiology that are otherwise invisible.