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Despite advances in ventilator management, 31% to 38% of patients with adult respiratory distress syndrome (ARDS) will die, some from progressive respiratory failure. Inability to adequately oxygenate patients with severe ARDS has prompted extensive efforts to identify what are now known as alternative modes of ventilation including high-frequency oscillatory ventilation and airway pressure release ventilation. Both modalities are based on the principles of the open-lung concept and aim to improve oxygenation by keeping the lung uniformly inflated for an extended period of time. Although a mortality benefit has not been proven, some patients may benefit from these alternative modes of ventilation as rescue measures while the underlying process resolves. The purpose of this article is to review the evidence and mechanisms underlying each modality and to describe the fundamental steps in initiating, adjusting, and terminating these modes of ventilation.