While the majority of patients can be easily weaned from mechanical ventilation, there are a substantial minority who pose considerable difficulty. These patients account for a disproportionate amount of health-care costs and pose enormous clinical, economic, and ethical problems. The major pathophysiological determinants of weaning outcome are psychological factors, efficacy of pulmonary gas exchange and the balance between respiratory neuromuscular capacity and respiratory load. A number of physiological indices are used to predict the optimal time to undertake a weaning trial; these include indices of oxygenation, maximum inspiratory pressure, vital capacity, thoracic compliance, minute ventilation, maximum voluntary ventilation, and the pattern of breathing. Weaning techniques that are commonly used include gradual t-tube trials, intermittent mandatory ventilation, pressure support ventilation, and abrupt discontinuation of ventilation support.