End-expiratory pressure remains one of the few parameters of mechanical respiratory support whose values have not been strictly regulated using the evidence-based approach. The absence of «gold standard» for end-expiratory pressure optimization together with its obvious significant contribution to the efficiency and safety of respiratory support has driven the search for the optimal method of choosing its values for several decades.Aim of the review: to identify the optimal methods for determining the values of end-expiratory pressure based on the analysis of its positive and negative effects in the used strategies of mechanical respiratory support.Material and methods. We analyzed 165 papers from the PubMed, Scopus, and RSCI databases of medical and biological publications. Among them we selected 86 sources that most completely covered the following subjects: respiratory support, end-expiratory pressure, recruitment, ventilation-perfusion relationships, metabolography, and gas analysis.Results. We outlined the main positive and negative effects of the end-expiratory pressure with regard to both lung biomechanical characteristics and pulmonary perfusion. The evolution of views on the methods of determining optimal values of the end-expiratory pressure was reviewed with the emphasis on a certain «fixation» of the scientific community in recent decades concerning the opening of the alveoli. The promising techniques based on the analysis of the diffusion capacity of the lungs were presented.Conclusion. Focusing on mechanical lung opening prevents the scientific community from advancing in the optimization of the end-expiratory pressure. Dynamic assessment of pulmonary diffusion efficiency provides a new perspective on the issue, offering additional ways to the development of «gold standard».