Mechanically ventilated patients are subject to few pathophysiologic disturbances that have such intuitive importance as abnormal function of the respiratory output. Abnormal function of the respiratory output plays a fundamental role in all aspects of mechanical ventilation: in determining which patients require mechanical ventilation, in determining the interaction between a patient and the ventilator, and in determining when a patient can tolerate discontinuation of mechanical ventilation. Monitoring indexes such as the rate of rise in electrical activity of the diaphragm, Po.1, (dP/dt)max, and Pmus, has provided insight into the performance of the respiratory centers in critically ill patients, but these methods require considerable refinement. A large body of research on measurements of energy expenditure of the respiratory muscles, such as pressure-time product, and measurements of inspiratory effort, such as the tension-time index, is currently accumulating. Several challenges, however, lay ahead regarding these indices. First, there is the need to identify the correct level of pressure generation and respiratory muscle effort that should be attained in the day-to-day management of mechanically ventilated patients. The correct titration of ventilator setting should not cause iatrogenic muscle damage because the support is excessive or insufficient. One of the challenges in reaching this goal is that for the same patient, different underlying pathologic conditions (eg, sepsis or ventilator-associated muscle injury) may require different levels of support. Second, many of the measurements of pressure generation and effort have been confined to the research laboratory. Modifications of the technology to achieve accurate measurements in the intensive care unit-outside of the research laboratory--are needed. To facilitate individual titration of ventilator settings, the new technologies must provide easier access to quantification of drive, pressure output, and effort. Finally, more research is needed to define the effect of monitoring respiratory output on patient outcome and containment of costs.