Mechanical ventilation is an important lifesaving intervention for critically ill patients with respiratory failure, generating air movement to ensure adequate ventilation and gas exchange. Critically ill patients on mechanical ventilation require specialized attention to the implementation of analgesia–sedation regimens to promote safe and comfortable use of mechanical ventilation and avoidance of associated complications. Critical care pharmacists play an important role in ensuring the appropriate and safe use of medications in this population. In this chapter, we review the basic principles of mechanical ventilation and details of its use in caring for critically ill patients.