Considering the increasing prevalence of obesity among the critically ill patient, mechanical ventilation of this type of patients has almost become a daily practice. However, no consensus regarding mechanical ventilation for obese patients has recently been published. Considering the particular pathophysiological features of respiratory system in obese patients, the risk of ventilator induced lung injury (VILI) is highly elevated. This narrative review aims to present the constrains related to mechanical ventilation in obese patients, as well as the features that predispose them to VILI. Moreover, the effects every determinant incriminated in VILI were described with application on the pathophysiological features of obese patients. Increased emphasis was placed on the newly concept of ergotrauma as one of the main determinants of VILI. This is one of the first reviews dedicated to the effects of mechanical power and ergotrauma on mechanically ventilated patients with obesity. Moreover, increased attention was given to the impact of biotrauma related to VILI, considering that the new concept of “pre-conditioning cloud” related to obesity has recently emerged.