Acute respiratory distress syndrome is a multifactorial lung injury that continues to be associated with high levels of morbidity and mortality. Mechanical ventilation, although lifesaving, is associated with new iatrogenic injury. Current best practice involves the use of small Vt, low plateau and driving pressures, and high levels of positive end-expiratory pressure. Collectively, these interventions are termed “lung-protective ventilation.” Recent investigations suggest that individualized measurements of pulmonary mechanical variables rather than population-based ventilation prescriptions may be used to set the ventilator with the potential to improve outcomes beyond those achieved with standard lung protective ventilation. This review outlines the measurement and application of clinically applicable pulmonary mechanical concepts, such as plateau pressures, driving pressure, transpulmonary pressures, stress index, and measurement of strain. In addition, the concept of the “baby lung” and the utility of dynamic in addition to static measures of pulmonary mechanical variables are discussed.