Intrathecal opioids are widely used as useful adjuncts in the treatment of acute and chronic pain, and a number of non-opioid drugs show promise as analgesic drugs with spinal selectivity. In this review we examine the historical development and current use of intrathecal opioids and other drugs that show promise for treating pain in the perioperative period. The pharmacology and clinical use of intrathecal morphine and other opioids is reviewed in detail, including dosing guidelines for specific surgical procedures and the incidence and treatment of side effects associated with these drugs. Available data on the use of non-opioid drugs that have been tested intrathecally for use as analgesics are also reviewed. Evidence-based guidelines for dosing of intrathecal drugs for specific surgical procedures and for the treatment of the most common side effects associated with these drugs are presented.