Respiratory muscle dysfunction associated with ventilatory loading may be partially attributed to respiratory muscle injury. Exertion-induced muscle injury can be defined as structural alterations of the muscle, however, a better understanding of the biochemical, morphologic, and functional correlates of injured respiratory muscles will facilitate discrimination of how injury, fatigue, and weakness contribute to respiratory muscle dysfunction. In addition to the increased loads associated with lung disease, many factors such as poor arterial blood gases, immobilization, sepsis, decreased nutrition, and corticosteroids may increase susceptibility to exertion-induced respiratory muscle injury. Respiratory muscle injury in humans is not well-described, however, more extensive evidence has been shown in animal models of increased ventilatory loading. Potential mechanisms of respiratory muscle injury are mechanical stress, metabolic stress, and inflammation. In order to optimize therapeutic interventions, a better understanding of these mechanisms and the patients that are most susceptible to respiratory muscle injury needs to be determined.