Drug delivery to the epidural and intrathecal space can provide relief of both acute and chronic pain. Various classes of medications can be used differentially to target chronic nociceptive or neuropathic pain. Food and Drug Administration (FDA) approved medications for pain treatment for intrathecal drug delivery devices are morphine and ziconotide currently. This chapter covers the intrathecal/epidural trial, baclofen, opioids, local anesthetics, alpha-2 agonists, ziconotide, gabapentinoids, and N-methyl-D-aspartate (NMDA) antagonists. Opioids remain important in neuraxial analgesia; they are of most effective for nociceptive pain but can be used for neuropathic pain. Ziconotide, a noncompetitive N-type calcium channel blocker, has shown efficacy in treating malignant as well as nonmalignant chronic pain and should be considered first-line therapy for intrathecal treatment of chronic pain.