The ventilator-induced diaphragmatic dysfunction is a group of disorders caused by the inactivity of the diaphragm muscle during controlled mechanical ventilation. From a structural point of view, the diaphragm subjected to mechanical ventilation undergoes an atrophy process, in which decreased synthesis and increased muscle protein degradation are observed. Recent research has identified different molecular signaling pathways that link both processes in the diaphragm, describing compelling evidence that shows that oxidative stress contributes to this phenomenon. Also, functional changes characterized by a reduction in stress and fatigue resistance, associated with an increase in the maximum shortening velocity are observed. The purpose of the present review is to analyze the impact of mechanical ventilation on the structure and function of the diaphragm muscle. Clinical implications and potential preventive steps are discussed. Since the duration of mechanical ventilation is the primary responsible for the absence of mechanical stimulation on the diaphragm, the use of ventilatory strategies for successful early weaning and early use of partial modalities should be the main pillars in the prevention of this condition.