Sedation and analgesia are central elements in the care of critically ill, mechanically-ventilated patients. The goal of analgesic therapy is to provide relief from pain and physical discomfort which may lead to poor sleep, agitation, or a stress response. Opioids, such as morphine, fentanyl, and hydromorphone, are considered first-line agents for treating pain. All of these agents are equally effective at equipotent doses and the choice of an agent depends on both drug and patient characteristics. Sedatives with amnestic properties are desirable to prevent or relieve anxiety and agitation. The benzodiazepines and propofol are the primary sedative agents used in the intensive care unit (ICU). Agents such as clonidine and haloperidol may have a role in the ICU when used concomitantly with sedatives and analgesics. An understanding of the pharmacotherapy of sedation and analgesia in the ICU will help support appropriate usage of these agents and improve patient care.