Although the administration of sedatives is a commonplace activity in the ICU, few guidelines are available to aid the clinician in this practice. The first principle of sedative administration is to define the specific problem requiring sedation and to rationally choose the drug and depth of sedation appropriate for the indication. Next, the clinician must recognize the diverse and often unpredictable effects of critical illness on drug pharmacokinetics and pharmacodynamics. Failure to recognize these effects may lead initially to inadequate sedation and subsequently to drug accumulation. Drug accumulation may result in prolonged encephalopathy and mechanical ventilation and may mask the development of neurologic or intra-abdominal complications. Daily interruption of continuous sedative infusions is a simple and effective way of addressing this problem. A glossary of sedative drugs commonly used in the ICU is included in this review.