Various clinical situations may arise in the PICU that necessitate the use of sedation, analgesia, or both. Although there is a large clinical experience with midazolam in the PICU population and it remains the most commonly used benzodiazepine in this setting, lorazepam may provide an effective alternative, with a longer half-life and more predictable pharmacokinetics without the concern of active metabolites. However, there are limited reports regarding its use in the PICU population, and concerns exist regarding the potential for toxicity related to its diluent, propylene glycol. Although the synthetic opioid fentanyl frequently is chosen for use in the PICU setting because of its hemodynamic stability, preliminary data suggest morphine may have a slower development of tolerance and may cause fewer withdrawal symptoms than fentanyl. Morphine's safety profile includes long-term follow-up studies that have demonstrated no adverse central nervous system developmental effects from its use in neonates and infants. In the critically ill infant at risk following surgery for congenital heart disease, clinical experience supports the use of the synthetic opioids, given their ability to modulate PVR and prevent pulmonary hypertensive crisis. Alternatives to the benzodiazepines and opioids include ketamine, pentobarbital, or dexmedetomidine. Ketamine may be useful for patients with hemodynamic instability or airway reactivity. There are limited reports regarding the use of pentobarbital in the PICU, with one study raising concerns of a high incidence of adverse effects associated with its use. Propofol has gained great favor in the adult population as a means of providing deep sedation while allowing for rapid awakening; however, its routine use is not recommended because of its potential association with "propofol infusion syndrome." As the pediatric experience increases, it appears that there will be a role for newer agents such as dexmedetomidine.