Our current understanding of protective measures for avoiding ventilator-induced lung injury (VILI) has evolved from targeting low tidal volumes to lowering plateau and driving pressure. Even when pressures across the lung are reliably estimated, however, pressures alone cannot accurately gauge the injury risk; apart from flow rate, inspired oxygen fraction, and currently unmeasurable features of the mechanical microenvironment such as geometry, structural fragility, and vascular perfusion, the frequency with which high-risk tidal cycles are applied must help determine the intensity of potentially damaging energy application. Recognition of a strain threshold for damage by transpulmonary pressure, coupled with considerations of total energy load and strain intensity, has helped shape the unifying concept of VILI generation dependent upon the power transferred from the ventilator to the injured lungs. Currently, under-recognized contributors to the injury process must be addressed to minimize the risk imposed by ventilatory support.