Novel H1N1 swine origin influenza virus has led to a worldwide pandemic. During the pandemic, a significant number of patients became critically ill primarily because of respiratory failure. Most of these patients required intubation and mechanical ventilation and were treated with conventional modes of mechanical ventilation using a lung-protective strategy with low tidal volumes, plateau pressures <30 to 35 cm H2O, and optimal positive end-expiratory pressure. In some patients with persistent hypoxemia, alternative modes of ventilation, such as high-frequency oscillatory ventilation and airway pressure release ventilation, were used. We review the ventilatory management, recruitment maneuvers, prone positioning, and goals of ventilatory therapy for hypoxemic respiratory failure in general, as well as lessons learned in the management of H1N1-related respiratory failure.