Palliative care patients are predisposed to complex pain, including refractory pain, neuropathic pain, opioid-induced hyperalgesia, and opioid-induced neurotoxicity. Palliative care complex pain management can include use of subanesthetic parenteral ketamine. Support for subanesthetic ketamine exists from anecdotal experiences and nonrandomized studies, but there is a lack of statistically significant evidence to support or dismiss its use. Ketamine is sought for illegal, nonmedical purposes, so the lack of evidence coupled with potential for exploitation makes judicious and knowledgeable use critical. Palliative care nurse practitioners, as experts in symptom management, should evaluate and consider all potentially beneficial treatment strategies for complex pain, including novel strategies such as subanesthetic ketamine treatment. Several databases and clinical guideline repositories, along with inspection of germane articles' reference lists, were utilized to collect original research, retrospective studies, literature reviews, and case reports pertinent to the management of palliative care complex pain with parenteral ketamine. In conclusion, the evidence-based clinical decision-making process is engaged to outline a method to weigh the risks versus benefits of subanesthetic ketamine for this population of patients.