For patients with acute respiratory insufficiency, mechanical ("invasive") ventilation is a fundamental therapeutic measure to ensure sufficient gas exchange. Despite decades of strong research efforts, central questions on mechanical ventilation therapy are still answered incompletely. Therefore, many different ventilation modes and settings have been used in daily clinical practice without scientifically sound bases. At the same time, implementation of the few evidence-based therapeutic concepts (e.g., "lung protective ventilation") into clinical practice is still insufficient. The aim of our guideline project "Mechanical ventilation and extracorporeal gas exchange in acute respiratory insufficiency" was to develop an evidence-based decision aid for treating patients with and on mechanical ventilation. It covers the whole pathway of invasively ventilated patients (including indications of mechanical ventilation, ventilator settings, additional and rescue therapies, and liberation from mechanical ventilation). To assess the quality of scientific evidence and subsequently derive recommendations, we applied the Grading of Recommendations, Assessment, Development and Evaluation method. For the first time, using this globally accepted methodological standard, our guideline contains recommendations on mechanical ventilation therapy not only for acute respiratory distress syndrome patients but also for all types of acute respiratory insufficiency. This review presents the two main chapters of the guideline on choosing the mode of mechanical ventilation and setting its parameters. The guideline group aimed that - by thorough implementation of the recommendations - critical care teams may further improve the quality of care for patients suffering from acute respiratory insufficiency. By identifying relevant gaps of scientific evidence, the guideline group intended to support the development of important research projects.