The act of breathing depends on coordinated activity of the respiratory muscles to generate subatmospheric pressure. This action is compromised by disease states affecting anatomical sites ranging from the cerebral cortex to the alveolar sac. Weakness of the respiratory muscles can dominate the clinical manifestations in the later stages of several primary neurologic and neuromuscular disorders in a manner unique to each disease state. Structural abnormalities of the thoracic cage, such as scoliosis or flail chest, interfere with the action of the respiratory muscles-again in a manner unique to each disease state. The hyperinflation that accompanies diseases of the airways interferes with the ability of the respiratory muscles to generate subatmospheric pressure and it increases the load on the respiratory muscles. Impaired respiratory muscle function is the most severe consequence of several newly described syndromes affecting critically ill patients. Research on the respiratory muscles embraces techniques of molecular biology, integrative physiology, and controlled clinical trials. A detailed understanding of disease states affecting the respiratory muscles is necessary for every physician who practices pulmonary medicine or critical care medicine.