Weaning failure is, unfortunately, a rather common phenomenon for mechanically-ventilated patients (especially those with chronic obstructive pulmonary disease (COPD)), and the respiratory muscles play a pivotal role in its development. Weaning fails whenever an imbalance exists between the ventilatory needs and the neurocardiorespiratory capacity. This can happen if there is an increase in the energy demands of the respiratory muscles, a decrease in the energy available, a decrease in neuromuscular competence, or if the respiratory muscles pose an impediment to the heart and blood flow. The imbalance created will lead to weaning failure through the development of respiratory muscle fatigue, hypercapnia, dyspnoea, anxiety and organ dysfunction.