Mechanical ventilation associated lung injury (VALI) negatively impacts the outcomes of critically ill patients. Research during the past two decades has led to a better understanding of key physiologic mechanisms of injury, yet uncertainty over the topographical distribution of these mechanisms continues to fuel controversies over "best ventilation practice" in injured lungs. In this issue Pavone and colleagues have explored the temporal and spatial evolution of VALI in an elegant use of intravital microscopy. Their findings reinforce the notion that regions which receive most of the inspired gas, in Pavone's case the non-dependent lung of a rat supported in the lateral decubitus posture, are particularly susceptible to injury. However, the inability to measure tissue strain remote from the pleura keeps important questions about small scale intra-acinar stress and strain distributions unanswered.