Over the past 2 decades, the art of “weaning” from mechanical ventilation has been informed by increasing published basic science and outcomes studies. Although monitoring technologies can provide vast amounts of information before, during, and after liberation from mechanical ventilation, little data exists on how to maximally harness even routinely monitored, basic physiologic parameters. Overdependence on technology and derived variables, without data to demonstrate benefit, may even inhibit the patient’s progress if it is used inappropriately. We review the scientific evidence for best using routinely available physiologic data and a few more sophisticated and invasive monitoring technologies during weaning. We also suggest future study designs that would better inform the process of liberation from the ventilator and endotracheal extubation.