Mesenchymal stem/stromal cells (MSCs) offer considerable promise as a novel therapeutic strategy for acute respiratory distress syndrome (ARDS). MSCs may be able to "reprogramme" the immune response to reduce destructive inflammatory elements while preserving the host response to pathogens. In addition, MSCs may be able to enhance the repair and resolution of lung injury. Resolution of ARDS is impeded by destruction of the integrity of the epithelial barrier, which inhibits alveolar fluid clearance and depletes surfactant. MSCs appear to restore epithelial and endothelial function, via both paracrine and cell contact dependent effects. ARDS is frequently a component of a generalized process resulting in dysfunction and failure of multiple organs. MSCs have been demonstrated to decrease injury and/or restore function in other organs, including the kidney, liver and heart. MSCs may directly attenuate bacterial sepsis, the commonest and most severe cause of ALI/ARDS. The fact that MSCs are in clinical studies for a wide range of disease processes is a clear advantage for translating MSCs to clinical testing in patients with ARDS. However, some important knowledge gaps exist that may impede clinical translation. The ultimate success of MSCs as a therapy for patients with ARDS will likely be dependent on a greater knowledge of their mechanisms of action and the determination of the optimal strategies for their use in the clinical setting.