The respiratory muscles constitute a pump as vital to life as the heart. In patients with severe lung disease, the work of breathing is increased greatly, whereas the capacity of the respiratory muscles to generate tension and ventilation is impaired. In these circumstances, respiratory muscle fatigue may occur. When the cardiac pump fails, it often is possible to improve its performance by drug therapy with inotropic agents. In recent years, attention has been focused on the possibility of enhancing respiratory muscle function with drugs. The agents most studied have been the methylxanthines, theophylline and aminophylline. In vitro studies have demonstrated an inotropic effect of theophyllines on all skeletal muscles tested, including the diaphragm. The effect of theophyllines on skeletal muscle is dose related and animal studies show that any effect in humans, where dosage is limited by toxicity, is likely to be small. Early studies in humans showed a substantial positive inotropic effect on the diaphragm, but subsequently, a large number of studies have yielded mixed results. Up to the present time, most studies have failed to demonstrate a positive action of theophyllines. Although is it possible that these drugs may have a very small beneficial effect on contractility, not easily detected by the methods of some investigators, such as small effect of potentially toxic drugs is likely to be of limited clinical value.