The stress response to critical illness can have many deleterious effects. Appropriate use of sedation and analgesia can attenuate the stress response, alleviate pain and anxiety, and improve compliance with care. Agitation responds best to anxiolytic drugs; pain is best relieved by analgesics. A combination of these drugs can act synergistically, because most analgesics provide some degree of sedation. In select cases, neuromuscular blocking agents are required, but they should not be used without concomitant sedation and analgesia. Use of agents needs to be tailored to the needs of individual patients; indications, anticipated length of need, and underlying organ system derangements are important considerations.