Pharmacologic administration of sedatives is used routinely in the care of the critically ill to enhance patient comfort and optimize care. Long-term administration of NMB drugs is far less frequent but often occurs in patients with greater organ dysfunction. The experience of several authors using NMB drugs in the ICU is summarized in Table 5. Both classes of drugs have potential untoward effects. Some are readily predictable; others are not. NMB drugs enjoy a long record of safe, effective use during the perioperative period, but certain issues linger in defining appropriate administration to critically ill patients. Major concerns focus on the appropriate drug selection and delivery, monitoring, and neuromuscular recovery of patients who receive NMB drugs for longer than 24 hours. The development of myopathy and paresis has been increasingly recognized after prolonged use of NMB drugs in the ICU. Further investigation needs to fully characterize this process, identify those at risk, and outline a mechanism to prevent or limit the injury. Prolonged weakness may occur secondary to changes in the basic pharmacology and elimination of NMB drugs in ICU patients. Pathophysiologic changes in the nerve, muscle, or neuromuscular junction may also play a role in the development of some cases of prolonged weakness or myopathy after discontinuation of NMB drugs. Concerns about the potential for direct or indirect toxicity of NMB drugs to skeletal muscle and in the CNS remain. Resolution of these issues will improve the selection and optimal administration of sedative and NMB drugs in the ICU setting.