Prone position ventilation (PPV) is a technique of respiratory support for patients under a prone position. PPV has the advantages of promoting collapsed alveolar recruitment, enhancing ventilation/perfusion ratio, improving respiratory system compliance, facilitating secretion drainage, and reducing ventilator-associated lung injury. However, there is no unified recommendations for the timing of PPV initiation. For patients with moderate and severe ARDS, PPV is now recommended by guidelines for mechanical ventilation of acute respiratory distress syndrome (ARDS). Considering that ventilator-associated lung injury complicates ARDS, PPV should be implemented as soon as possible for patients with traditional ARDS. For those receiving extracorporeal membrane oxygenation (ECMO), it is recommended to start PPV at the early stage of ECMO support in ECMO centers. The timing of PPV for intubated COVID-19 patients with poor respiratory compliance can refer to patients with traditional ARDS. The timing for awake PPV in COVID-19 gradually moves forward. Even if oxygenation does not dramatically drop, PPV can be started in COVID-19 patients as long as they are tolerable and have no contraindications.