Diaphragm dysfunction is increasingly common in mechanically ventilated patients, with its etiology arising from several possible mechanisms of injury or myotrauma. These injuries can be classified into four categories: (1) over-assistance myotrauma, (2) under-assistance myotrauma, (3) eccentric myotrauma, and (4) expiratory myotrauma, all of which influence the weaning process. In over-assistance myotrauma, the diaphragm becomes unloaded due to excessive support from the ventilator or suppression of patient efforts, leading to myofibrillar atrophy. Maintaining some level of patient effort through assisted modes of ventilation, phrenic nerve stimulation, or reducing sedation may help alleviate ventilator-induced diaphragmatic atrophy. Under-assistance myotrauma arises from insufficient ventilatory support or inadequate unloading of the diaphragm, which may predispose it to injury. Eccentric myotrauma occurs when the diaphragm contracts under lengthened conditions, often during patient-ventilator asynchronies. Finally, expiratory myotrauma involves the application of excessive positive end-expiratory pressure (PEEP), which impairs diaphragm length relationships and results in sarcomere dropout (longitudinal atrophy). This may necessitate a gradual reduction in PEEP during the weaning process. This chapter focuses on the basic and clinical evidence for these types of myotrauma and their potential impact on weaning.