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Ventilator-associated pneumonia (VAP) is a lung infection commonly acquired following tracheal intubation. This review assesses the role of the supine semirecumbent and the prone position as VAP preventive strategies and calls attention for further investigation on novel body positions that could potentially reduce risks of VAP.The most recent studies on the semirecumbent position failed to achieve an orientation of the head of the bed higher than 30° and did not corroborate any benefit of the semirecumbent position on VAP, as reported in earlier studies. To date, there is clear evidence that the supine horizontal body position increases risks of pulmonary aspiration and VAP, particularly when patients are enterally fed. Laboratory reports are emphasizing the importance of an endotracheal tube–oropharynx–trachea axis below horizontal to avoid VAP. The prone position potentially increases drainage of oropharyngeal and airways secretions and recent evidence is supporting its beneficial effects. However, several associated adverse effects preclude its regular use as a VAP preventive strategy for patients other than those with acute respiratory distress syndrome.Body position greatly affects several pathogenetic mechanisms of VAP. The current evidence recommends avoidance of supine horizontal position in order to prevent aspiration of colonized gastric contents. The semirecumbent position has proven benefits and should be routinely used but there is still limited evidence to recommend the lowest orientation of the bed at which the patient can be safely maintained. Results from pioneering laboratory investigation call attention to new possible positions, that is lateral Trendelenburg position, aimed to avoid pulmonary aspiration and to enhance mucus clearance in intubated patients.