Opioid analgesics are crucial for pain management in most patients receiving palliative care. Contemporary models advocate for the provision of palliative care services as early as possible in a course of illness, suggesting that many patients will receive palliative care services, and opioids, concurrent with complex disease-modifying therapies. This article reviews the metabolic pathways of commonly prescribed opioid analgesics and provides a survey of what is known about how disease-modifying therapies alter the pharmacokinetics and pharmacodynamics of opioids. Existing treatment guidelines are reviewed. Practical suggestions are offered.