The stay in an ICU is a complex mixture of providing optimal care while keeping the patient safe. Means of reducing the anxiety associated with the ICU stay include frequent reorientation and maintenance of patient comfort with sedation supplemented by analgesia as needed. The most common agents used to provide sedation include benzodiazepines, propofol, and the newer dexmedetomidine. Others include barbiturate agents, neuroleptics, clonidine, etomidate, ketamine, and supplemental opioid analgesics for pain control. A common complication of sedation is tolerance, which can lead to withdrawal if the sedation is discontinued hastily. This article evaluates the occurrence of tolerance and withdrawal in the most commonly used sedatives in critically ill patients.