Common medical conditions that require mechanical ventilation include chronic obstructive lung disease, acute lung injury, sepsis, heart failure, drug overdose, neuromuscular disorders, and surgery. Although mechanical ventilation can be a life saving measure, prolonged mechanical ventilation can also present clinical problems. Indeed, numerous well-controlled animal studies have demonstrated that prolonged mechanical ventilation results in diaphragmatic weakness due to both atrophy and contractile dysfunction. Importantly, a recent clinical investigation has confirmed that prolonged mechanical ventilation results in atrophy of the human diaphragm. This mechanical ventilation-induced diaphragmatic weakness is important because the most frequent cause of weaning difficulty is respiratory muscle failure due to inspiratory muscle weakness and/or a decline in inspiratory muscle endurance. Therefore, developing methods to protect against mechanical ventilation-induced diaphragmatic weakness is important.