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The recent H1N1 epidemic has resulted in a large number of deaths, primarily from acute hypoxemic respiratory failure. We reviewed the current strategies to rescue patients with severe hypoxemia. Included in these strategies are high-frequency oscillatory ventilation, airway pressure release ventilation, inhaled vasodilators, and the use of extracorporeal life support. All of these strategies are targeted at improving oxygenation, but improved oxygenation alone has yet to be demonstrated to correlate with improved survival. The risks and benefits of these strategies, including cost-effectiveness data, are discussed.