Ventilation is inherently a dynamic process. The present-day clinical practice of concentrating on the static inflation characteristics of the individual tidal cycle (plateau pressure, positive end-expiratory pressure, and their difference [driving pressure, the ratio of Vt to compliance]) does not take into account key factors shown experimentally to influence ventilator-induced lung injury (VILI). These include rate of airway pressure change (influenced by flow amplitude, inspiratory time fraction, and inspiratory inflation contour) and cycling frequency. Energy must be expended to cause injury, and the product of applied stress and resulting strain determines the energy delivered to the lungs per breathing cycle. Understanding the principles of VILI energetics may provide valuable insights and guidance to intensivists for safer clinical practice. In this interpretive review, we highlight that the injuring potential of the inflation pattern depends upon tissue vulnerability, the number of intolerable high-energy cycles applied in unit time (mechanical power), and the duration of that exposure. Yet, as attractive as this energy/power hypothesis for encapsulating the drivers of VILI may be for clinical applications, we acknowledge that even these all-inclusive and measurable ergonomic parameters (energy per cycle and power) are still too bluntly defined to pinpoint the precise biophysical link between ventilation strategy and tissue injury.