This chapter focuses on the use of capnography to optimize and minimize the length of mechanical ventilation. Mechanical ventilation can be divided into three phases: acute stabilization, pre-weaning, and weaning/ extubation readiness testing. Alveolar minute ventilation is determined from the volumetric capnogram. Liberation from mechanical ventilation implies the use of an extubation readiness test to withdraw mechanical ventilation as soon as the patient meets extubation criteria regardless of the level of ventilatory support. A myriad of adversities make weaning and liberation from mechanical ventilation an extremely important clinical issue. With the majority of intensive care unit (ICU) patients requiring mechanical ventilation, minimizing the duration of mechanical ventilation while optimizing the potential for successful extubation is crucial in the management of critically ill patients. Capnography, both time-based and volumetric, allows mechanical ventilatory strategies to be designed with clear, precise, objective criteria.