Successful management of chronic cancer and nonmalignant pain remains a challenge to clinicians, and cost effectiveness is an important consideration for clinical decision making. Although the oral route was previously considered the optimal method of chronic opioid administration, emerging evidence demonstrates a therapeutic advantage to intrathecal opioid delivery compared to alternative modalities. Intrathecal drug delivery uses an implantable drug infusion system to deliver very low doses of opioids and other analgesics directly into the intrathecal space. Although the initial costs of surgical implantation of an intrathecal pump appear to be substantial, maintenance costs of intrathecal drug delivery over time are significantly lower than other routes of administration, including oral and intravenous drug delivery. Cost analyses of alternate routes of opioid administration indicate that intrathecal delivery is the most cost-effective route of opioid administration for patients who require long-term management of cancer (≥ 3–6 months) or nonmalignant pain (≥ 11–22 months).