The interaction between a patient and a ventilator is the major determinant of the amount of respiratory muscle rest achieved by the machine. We are beginning to acquire a better understanding of the mechanisms that underlie this complex interaction, but this information has yet to be integrated into the routine clinical management of ventilator-supported patients. To achieve that goal, we need better techniques of detecting and monitoring patient-ventilation asynchrony, and the development of simple algorithms that can minimize its occurrence. Finally, research is needed to determine the occurrence and importance of respiratory muscle fatigue during failed weaning attempts so as to better guide the timing and pace of the weaning process in problematic patients.