<p>Lung-protective ventilation is the current standard for mechanical ventilation of patients with acute respiratory distress syndrome (ARDS). Traditionally, this approach has focused on the controlled phase of mechanical ventilation, but emerging data suggest that how patients are managed during assisted ventilation may also impact clinical outcomes. Experimental and observational clinical data indicate that excessive respiratory effort may further damage already injured lungs and may also lead to diaphragm myotrauma. Conversely, insufficient effort and prolonged passive ventilation are associated with diaphragm atrophy and dysfunction. Recent non-invasive techniques to monitor respiratory drive and effort at the bedside have facilitated the development of a new strategy to protect both the lungs and the diaphragm. The lung- and diaphragm-protective (LDP) ventilation framework highlights the need to better integrate ventilation and sedation strategies to facilitate timely and safe spontaneous breathing. This new paradigm has driven the development of emerging supportive and therapeutic modalities, such as diaphragm neurostimulation and partial neuromuscular blockade. Clinical trials are needed to evaluate the impact of LDP strategies on patient-centered outcomes, using designs that account for the possibility of heterogeneity of treatment effect in the ARDS population. In this review, we summarize the physiological background for the LDP framework, as well as the current clinical evidence evaluating this strategy.</p> Visual abstract <p></p>