Sedation and analgesia are important components of care for the mechanically ventilated patient in the intensive care unit (ICU). An understanding of commonly used medications is essential to formulate a sedation plan for individual patients. The specific physiological changes that a critically ill patient undergoes can have direct effects on the pharmacology of drugs, potentially leading to interpatient differences in response. Objective assessments of pain, sedation, and agitation have been validated for use in the ICU for assessment and titration of medications. An evidence-based strategy for administering these drugs can lead to improvements in short- and long-term outcomes for patients. In this article, we review advances in the field of ICU sedation to provide an up-to-date perspective on management of the mechanically ventilated ICU patient.