The current understanding of lung mechanics and ventilator-induced lung injury suggests that patients who have acute respiratory distress syndrome should be ventilated in such a way as to minimize alveolar over-distension and repeated alveolar collapse. Clinical trials have used such lung protective strategies and shown a reduction in mortality; however, there is data that these “one-size fits all” strategies do not work equally well in all patients. This article reviews other methods that may prove useful in monitoring for potential lung injury: exhaled breath condensate, pressure-volume curves, and esophageal manometry. The authors explore the concepts, benefits, difficulties, and relevant clinical trials of each.