Despite recent advances in understanding, the management of acute respiratory distress syndrome (ARDS) remains a challenging clinical problem. Optimization of gas exchange and preventing the iatrogenic propagation of lung injury are cornerstones of its clinical management. A number of novel approaches and adjuncts to mechanical ventilation have been described over the past decade to help achieve these goals, and some have been widely implemented with varying degrees of success. This chapter will review the rationale and evidence supporting the use of such adjunctive strategies.