This article first reviews the evidence for and against chronic opioid therapy. Evidence supporting the opioid responsiveness of chronic pain, including neuropathic pain, includes multiple randomized trials conducted over months (up to 8 months). Observational studies are conducted for longer, and many also support opioid analgesic efficacy. Concerns have arisen about loss of efficacy with prolonged use, possibly related to tolerance or opioid-induced hyperalgesia. Mechanisms of tolerance and opioid-induced hyperalgesia are explored. Evidence on other important outcomes such as improvement in function and quality of life is mixed, and is less convincing than evidence supporting analgesic efficacy. It is clear from current evidence that many patients abandon chronic opioid therapy because of the unacceptability of side effects. There are also concerns about toxicity, especially when opioids are used in high doses for prolonged periods, related to hormonal and immune function. The issue of addiction during opioid treatment of chronic pain is also explored. Addiction issues present many complex questions that have not been satisfactorily answered. Opioid treatment of pain has been, and remains, severely hampered because of actual and legal constraints related to addiction risk. Pain advocacy has focused on placing addiction risk into context so that addiction fears do not compromise effective treatment of pain. On the other hand, denying addiction risk during opioid treatment of chronic pain has not been helpful in terms of providing physicians with the tools needed for safe chronic opioid therapy. Here, a structured goal-directed approach to chronic opioid treatment is suggested; this aims to select and monitor patients carefully, and wean therapy if treatment goals are not reached. Chronic opioid therapy for pain has not been a universal success since it was re-established during the last two decades of the twentieth century. It is now realized that the therapy is not as effective or as free from addiction risk as was once thought. Knowing this, many ethical dilemmas arise, especially in relation to patients' right to treatment competing with physicians' need to offer the treatment selectively. In the future, we must learn how to select patients for this therapy who are likely to achieve improvement in pain, function and quality of life without interference from addiction. Efforts will also be made in the laboratory to identify opioids with lower abuse potential.