Although the majority of patients can be easily weaned from mechanical ventilation, a substantial minority pose considerable difficulty. These patients account for a disproportionate amount of health care costs, and they pose enormous clinical, economic, and ethical problems. The major determinants of weaning outcome include the adequacy of pulmonary gas exchange, respiratory muscle pump function, and psychological problems. Many of the physiologic indices that have been used to predict weaning outcome are frequently inaccurate. Several techniques of weaning can be used, and there are no data to suggest the superiority of one technique over another. Management of the problem patient should be directed at the underlying cause of ventilator dependency, and an organized plan should be followed.