Recently, there has been renewed interest in high-frequency oscillatory ventilation (HFOV) as a lung-protective strategy in adults. It limits overdistension and prevents cyclic collapse by maintaining end-expiratory lung volume. Studies have shown that HFOV is safely tolerated in the adult population and may offer more benefit if applied early in the course of disease. These findings have implications for clinicians as the use of HFOV may increase in the coming decade. Gas transport mechanisms, ventilator settings, patient monitoring, and clinical considerations for HFOV are substantially different from conventional mechanical ventilation. This article reviews management strategies and monitoring priorities currently recommended for management of adults receiving HFOV.