The authors apply eight ethical domains of analysis to the question of treatment of chronic pain with opioids in patients with histories of substance use disorders: autonomy, nonmaleficence, beneficence, justice, medical condition, patient preference, quality of life, and consideration of specific individual or sociocultural issues. These eight domains are drawn from principle-based and case-based ethical perspectives. The domains are developed by review of available literature and through application to a specific presented case. Factors that interfere with rational, ethical decision-making regarding opioid pain management are identified. Chronic pain and substance use disorders share a history of stigmatization, underdiagnosis, and undertreatment. Using the presented case as a point of departure, the authors discuss principles for prescription of opioids for treatment of chronic noncancer pain in the setting of history of substance use disorders.