Introduction 1 2 2 3 4 5 6 7 In the present review of the literature we describe the intrinsic mechanisms that explain how MV inflicts alveolar damage and the controversy regarding the use of RMs as an adjunct to MV. Finally, we discuss the interactions between lung infection and periodic application of high intrathoracic pressure, both in experimental models of ALI and in patients with ARDS. Method To identify the most relevant English language publications, the Medline database was searched using the following keywords: mechanotransduction, acute lung injury, acute respiratory distress syndrome, mechanical ventilation, ventilator-induced lung injury, overdistension, recruitment maneuvers, and bacterial translocation. 1 Intrinsic mechanism of ventilator-induced lung injury 2 8 10 11 12 13 14 Experimental evidence on recruitment maneuvers 15 16 2 1 17 15 18 2 19 20 21 In summary, the beneficial effects of RMs have been demonstrated in animal models of alveolar collapse induced by surfactant depletion. However, the pathobiology of ARDS is more complex and includes an altered vascular barrier function and alveolar flooding or consolidation. Indeed, in animal models other than that involving surfactant depletion, the effect of RMs on lung function is less evident. Role of recruitment maneuvers in anesthetized patients 22 22 2 5 23 24 25 26 27 Recruitment maneuvers in patients with acute respiratory distress syndrome 3 28 29 2 2 6 30 31 32 33 2 2 34 35 36 37 38 3 39 40 31 41 42 43 In summary, RMs can be useful in improving oxygenation in patients receiving MV with low PEEP and low tidal volume. However, in patients with ARDS receiving MV with high PEEP levels, the beneficial effects of RMs disappear. RMs may restore lung volume and oxygenation in endotracheal suctioning-induced lung derecruitment in mechanically ventilated patients diagnosed with ALI/ARDS. RMs should be avoided in patients with suspected or documented intracranial hypertension, in patients with a stiff chest wall, and in patients in the late stage of ARDS. Lung infection and mechanical ventilation ex vivo  44 45 46 47 48 49 50 51 52 53 54 Pseudomonas aeruginosa  55 Conclusion On the basis of our review of the literature on experimental and clinical studies, considerable uncertainty remains regarding the use of RMs in humans with ARDS. RMs may have a role to play in patients with early ARDS and normal chest wall mechanics because there is great potential for alveolar recruitment, and after disconnections from the ventilator, when sudden loss of lung volume promotes alveolar instability and derecruitment. Recommendations to use RMs as adjuncts during lung protection ventilatory strategies seem unnecessary because sustained improvements in lung function have not been found when the strategies are combined. The presence of lung infection must be considered a major limitation for aggressive RMs because translocation of bacteria and the occurrence of systemic sepsis have been demonstrated in animal models. Finally, large randomized studies do not support the use of RMs in patients with ARDS. In conclusion, the use of RMs cannot be recommended in the light of current knowledge, and if RMs are used they should be restricted to an individualized clinical decision or to a last resort to improve oxygenation and lung mechanics in a severely hypoxemic ARDS patient. Competing interests None declared. Abbreviations ALI = acute lung injury; ARDS = acute respiratory distress syndrome; MV = mechanical ventilation; PEEP = positive end-expiratory pressure; RM = recruitment maneuver; VILI = ventilator-induced lung injury.