Pleural effusion is a fluid collection within the pleural space and is a common finding in mechanically ventilated patients. It is frequently related to fluid overload, hyponcotic states, heart failure, and altered pleural pressure due to atelectasis or pneumonia. Recent literature has shown that its incidence within ARDS is increasing, even if, in most of cases, at least in the early phases, it seems of limited clinical relevance. Most of the knowledge of Pleural Effusion and of its interaction with lung/chest wall mechanics derives from a small number of experimental studies and from some clinical studies, in most of the cases performed with normal lung parenchyma. In ARDS, however, Pleural Effusion seems to have a little effect "per se" on tidal mechanics and oxygenation (increasing elastance and reducing PO2), that are already profoundly affected by the lung injury itself. To sum up all the observations, we can assume that Pleural Effusion alters regional transmural pressure, restricting more the inspiration phase, and creating an opening/closure effect that can be reverted by PEEP application in recruitable lungs. This restores volume and compliance only if the abdomen is normally expansible. Drainage of Pleural Effusion is frequently performed in ICU but the benefits and risks are not well established. Lung ultrasound is an effective technique with high sensitivity and specificity for both bedside diagnosis and drainage guidance. It may help to quantify and qualify the effusion and at the same time the grade of aeration of underling parenchyma. Aim of this review is to summarize the current evidence and opinions about the interaction between Pleural Effusion and positive pressure ventilation in the presence of ARDS, its impact on gas exchange and tidal mechanics, trying to figure out the best bedside management that is not available yet. The estimation of both lung and chest wall elastance may help in the clinical decision making whether to drain or not in order to improve respiratory mechanics and oxygenation. Further research is still needed to determine the effect of drainage on clinical outcome and to evaluate its application in the weaning strategies.