Patients with both chronic pain and substance use disorders are increasingly encountered in a variety of treatment settings. The treatment of these patients raises a number of ethical and patient care issues. Consultation-liaison psychiatrists possess the knowledge and skills to constructively address these issues. This chapter provides clinicians with a review of clinical and ethical dilemmas related to opioid treatment of chronic pain in patients with substance use disorders. The core conflict of beneficence and nonmaleficence will be explored in relation to the concepts of autonomy, justice, respect for persons, confidentiality, and informed consent. The thesis of this discussion focuses on the clinician's desire to provide compassionate care and relieve suffering, which sometimes conflicts with the clinician's desire to improve functioning, extend longevity, and enrich quality of life. A harm reduction model for clinical decision making is summarized.