A decade after the introduction of lung-protective ventilation strategies with low tidal volumes, the adverse effects of mechanical ventilation remain a scientific and clinical challenge. This situation has fueled the search for adjuvant pharmacological strategies to advance the benefit of protective ventilation in an additive or synergistic manner. In a recent issue of Critical Care, Müller and coworkers demonstrate convincingly that the initiation of high-dose simvastatin treatment prior to the onset of mechanical ventilation can attenuate adverse effects in overventilated mice. The present commentary discusses the need for adjuvant therapy in mechanical ventilation, the scientific rational for statin therapy in this context, and potential limitations for its implementation into clinical practice.