Esterase hydrolysis is a metabolic pathway that can be exploited to increase the rate of metabolism and elimination and so reduce the duration of the pharmacodynamic effects of drugs. Previously applied to &bgr;-adrenergic blocking agents and muscle relaxants, this concept was recently used to develop an esterase-metabolised opioid, remifentanil.Remifentanil has a predictable rapid onset, short duration and rapid offset of analgesic effect. This is likely to allow easy titration of analgesia to changing anaesthesia requirements during surgery. The metabolism of remifentanil by non-specific esterases in the blood and tissues prevents accumulation, even when given at high dosages over prolonged periods. Clinical recovery from anaesthesia is very rapid, irrespective of the age or physical status of the patient or the type or duration of surgery. In addition, the non-organ dependent elimination of remifentanil obviates the usual requirement for opioid dose adjustments in patients with hepatic impairment.Adverse events of remifentanil are those typical of μ-opioid receptor agonists, including respiratory depression, muscle rigidity, hypotension and bradycardia.Thus, the major benefits of remifentanil, the prototype esterase-metabolised opioid, are the achievement of intense, titratable intraoperative analgesia allowing for rapid clinical recovery without the risk of inducing recurrent postoperative respiratory depression. In addition, residual opioid activity disappears rapidly following discontinuation of the drug.