Patient-ventilator asynchrony (PVA) is a common problem in mechanically ventilated patients. PVA appears whenever a mismatch between the three physiologic variables characterizing spontaneous breathing (respiratory drive, ventilatory requirements, and timing of the breathing pattern) and the three technologic variables characterizing ventilator function (inspiratory trigger, delivery mechanism, and cycle-off criterion) occurs. Therefore, the optimization of mechanical ventilation derives from the coordination between the physiological variables of the patient and the technological ones of the ventilator. Consequentially, patient-ventilator synchrony is a goal that can be achieved by interpreting the ventilatory needs and mechanical characteristics of the respiratory system of each individual patient and setting the ventilator accordingly. The future developments of technologies aimed at detecting and solving problems concerning patient-ventilator interaction should be oriented toward this goal. This chapter reviews the different types of asynchronies, their underlying causes, and practical approaches to detecting, correcting, and preventing them.