Intrathecal therapy is an established treatment option for patients with severe chronic pain who do not receive adequate relief from less invasive methods. Ziconotide is the only nonopioid analgesic approved by the U.S. Food and Drug Administration for intrathecal administration. Ziconotide is approved for monotherapy only, but combination intrathecal therapy is considered an acceptable treatment option by experts in the field. When ziconotide is administered as monotherapy, the stability exceeds the refill intervals recommended in the ziconotide prescibing information. Compounding ziconotide with other intrathecal drugs speeds ziconotide degradation, but the stability loss does not increase patient risk for withdrawal symptoms, because ziconotide dose reductions are not associated with adverse effects and the drugs compounded with ziconotide remained stable in a series of studies. Results from in vitro studies suggest that the stability of ziconotide can be maximized by diluting commercial ziconotide formulations as little as possible, decreasing the concentration(s) of the drug(s) compounded with ziconotide, and compounding ziconotide with powders (rather than solutions) of other intrathecal drugs. Because oxygen speeds ziconotide degradation, removing dissolved oxygen by bubbling nitrogen through diluted or compounded solutions improves ziconotide stability. By incorporating these recommendations into standardized protocols for diluting and compounding ziconotide, clinicians can help ensure that patients receive safe and cost-effective intrathecal ziconotide treatment.