The purpose of this review is to describe the muscles of respiration, mechanisms that lead to their dysfunction, and unique features of the respiratory muscles that should be considered when designing testing and training protocols for patients with respiratory compromise. The diaphragm's unique shape is an important determinant of its function. Respiratory pathophysiology combined with systemic abnormalities may result in inspiratory muscle weakness, fatigue, and injury. The specificity of training principle, as it applies to respiratory muscle training in patients with respiratory compromise, will be described. Precautions related to this type of training will also be outlined. In conclusion, a better understanding of the mechanisms contributing to inspiratory muscle dysfunction will assist physical therapists in designing the most appropriate training programs. This article, along with the other articles in this focus on respiratory muscle training, will provide therapists with scientifically based guidelines for rehabilitation of patients with impaired respiratory muscle function.