Mechanical ventilation is the defining event of intensive care unit (ICU) management. Although it is a life saving intervention in patients with acute respiratory failure and other disease entities, a major goal of critical care clinicians should be to liberate patients from mechanical ventilation as early as possible to avoid the multitude of complications and risks associated with prolonged unnecessary mechanical ventilation, including ventilator induced lung injury, ventilator associated pneumonia, increased length of ICU and hospital stay, and increased cost of care delivery. This review highlights the recent developments in assessing and testing for readiness of liberation from mechanical ventilation, the etiology of weaning failure, the value of weaning protocols, and a simple practical approach for liberation from mechanical ventilation.