<p>Acute respiratory failure and the acute respiratory distress syndrome (ARDS) are characterized by profound spatial and temporal heterogeneity in lung aeration, mechanics, and inflammation. While mechanical ventilation is often vital to ensure gas exchange, it can also cause or worsen lung injury as a result of the superimposed mechanical stress due to the application of positive pressure on a heterogeneous parenchyma. Characterizing the lung microstructure and function at small length scales is essential for understanding the pathogenesis of ventilator-induced lung injury. This is a challenging task due to the complex architecture of the lung, to its constant motion and deformation with breathing and pulsatile blood flow, and its multiscale organization. Indeed, mechanical forces act on the components of the extracellular matrix and cells, acini, airways and blood vessels at the microscale to impact numerous biological processes. Beyond these effects, the global mechanical behavior and function of the lung emerge from this complex dynamic system. Because synchrotron radiation imaging techniques such as phase-contrast computed tomography (PC-CT), and K-edge subtraction CT (KES-CT), have a high spatial resolution, are quantitative, and are fast, they offer unique insights into the multiscale, dynamic behavior of the lung. These modalities enable mapping of regional ventilation, blood distribution, within-breath alveolar recruitment/derecruitment, airway closure, and tissue strain. This review explains synchrotron radiation imaging modalities, and discusses the findings in models of acute respiratory failure, their translational implications, as well as future areas of investigation.</p>