Respiratory mechanics describe the lung function through pressure and flow and the interplay between the two during the respiratory cycle. Derived indices are volume, compliance and resistance (Hess, Respir Care 59(11):1773–1794, 2014). Thoracic surgery in most cases requires the separation of the lungs in order to allow surgery of or near one lung and ventilation of the other lung, while the perfusion to the non-ventilated lung is continued. This has profound implications for the gas exchange and respiratory mechanics. The necessary opening of the pleural interface during thoracic surgery alters intra-thoracic lung volume. The collapsing lung is released from the outward “spring” of the chest wall and collapses towards residual volume (Lohser and Slinger, Anesth Analg 121(2):302–318, 2015). Furthermore, end-expiratory lung volume of the ventilated lung is reduced and perfusion–ventilation matching of the ventilated lung is changed. This berries additional potential sources of alveolar damage and development of hypoxemia compared with non-thoracic surgery (Ball et al., Eur J Anaesthesiol 35:724–726, 2018). Lung injury is the leading cause of death after thoracic surgery (Lohser and Slinger, Anesth Analg 121(2):302–318, 2015). The main iatrogenic risk factors are due to the ventilator settings: Volu- and atelectrauma resulting in the so called ventilator induced lung injury (VILI). Ventilation management during one-lung ventilation (OLV) involves the interplay between respiratory mechanics, patient lung function and patient body morphology. Profound knowledge of lung physiology in thoracic surgery is essential to choose the best ventilator settings to allow adequate gas exchange and protect the lungs from VILI.