The administration of hydrophilic opioids via a continuous infusion results in selective spinal analgesia with a low incidence of side effects. Lipophilic opioids may also be associated with spinal effects. However, the doses required to produce postoperative analgesia also produce plasma concentrations within the MEAC. Thus, in clinical practice it may not be possible to limit epidural doses of lipophilic opioids to those associated with spinal analgesia. Regardless of the mechanism of action, epidural administration of lipophilic opioids may offer no clinical advantages over the IV route. Notwithstanding, epidural administration of small doses of lipophilic opioids in combination with local anesthetics may offer significant clinical advantages over systemic administration of opioids alone. Dose-ranging studies will be necessary to determine the ideal concentrations of opioids and local anesthetics, as well as the ratios of the two drugs to obtain optimal analgesia with minimal incidence of side effects.