The controversy surrounding the long-term use of opioid drugs in patients with nonmalignant pain has intensified in recent years. This debate is driven by a new willingness to consider the potential benefits of an approach that has been traditionally rejected as invariably ineffective and unsafe. The published literature continues to be very limited, but a growing clinical experience, combined with a critical reevaluation of issues related to efficacy, safety, and addiction or abuse, suggests that there is a subpopulation of patients with chronic pain that can achieve sustained partial analgesia from opioid therapy without the occurrence of intolerable side effects or the development of aberrant drug-related behaviors. Future research must confirm this impression through controlled clinical trials and clarify those factors that may predict therapeutic success or failure. For the present, the clinician who contemplates this approach must have a clear grasp of the relevant issues and an understanding of the guidelines for treatment and monitoring that have proved useful in practice.