Weaning patients from mechanical ventilation constitutes a major portion of the workload in an intensive care unit, as over 40% of total ventilator time is consumed by the weaning process. Several pathophysiological mechanisms may be responsible for weaning failure, but the precise role of each is incompletely understood. Patients who fail a weaning trial commonly develop hypercapnia, which appears to be due to decreased tidal volume rather than a primary decrease in respiratory drive. Respiratory muscle performance is impaired as a result of dynamic hyperinflation and paradoxic motion of the rib cage and abdomen. Worsening of pulmonary mechanics will cause further embarrassment of the respiratory muscles. However, the clinical importance of respiratory muscle fatigue remains unclear. Afferent stimuli arising in the lung parenchyma, respiratory muscles, or as a consequence of impaired gas exchange will be transmitted to the respiratory control centers and result in severe dyspnea in patients who fail a weaning trial.