Withdrawal from mechanical ventilation (or weaning) is one of the most common procedures in intensive care units. Almost 20 years ago, we published one of the seminal papers on weaning in which we showed that the best method for withdrawal from mechanical ventilation in difficult-to-wean patients was a once-daily spontaneous breathing trial with a T-piece. Progress has not stood still, and in the intervening years up to the present several other studies, by our group and others, have shaped weaning into an evidence-based technique. The results of these studies have been applied progressively to routine clinical practice. Currently, withdrawal from mechanical ventilation can be summarized as the evaluation of extubation readiness based on the patient's performance during a spontaneous breathing trial. This trial can be performed with a T-piece, which is the most common approach, or with continuous positive airway pressure or low levels of pressure support. Most patients can be disconnected after passing the first spontaneous breathing trial. In patients who fail the first attempt at withdrawal, the use of a once-daily spontaneous breathing trial or a gradual reduction in pressure support are the preferred weaning methods. However, new applications of standard techniques, such as noninvasive positive pressure ventilation, or new methods of mechanical ventilation, such as automatic tube compensation, automated closed-loop systems, and automated knowledge-based weaning systems, can play a role in the management of the patients with difficult or prolonged weaning.