Agitation, pain, and delirium are focal points for targeted pharmacologic therapy in the intensive care unit. Understanding how to treat these essential entities necessitates fundamental understanding of the pharmacology of sedation, analgesia, and antipsychotics. Monitoring the effectiveness of these medications is crucial to optimize therapeutic outcomes and minimize untoward effects. Agents used in the management of agitation include drugs that target γ-aminobutyric acid A such as benzodiazepines and propofol and those with other targets such as dexmedetomidine and ketamine. Analgesia in the intensive care unit is controlled primarily using intravenous opioids, which differ on the basis of their potencies and pharmacokinetics. The management of delirium involves preventing its occurrence, removing potential causes, and pharmacotherapy with antipsychotics. Finally, the introduction of paralysis with the use neuromuscular blockers is often necessary in critically ill patients in various situations. In addition to understanding pharmacologic principles associated with the treatment of agitation, pain, and delirium, familiarization with the plethora of assessment tools used to guide therapy in these critically ill patients is mandated. This review focuses on the pharmacology of therapeutic agents used for sedation, analgesia, delirium, and neuromuscular blockade. Significant focus is given to the various assessment tools often used in practice today.