Clinical experience supports the notion that opioids can be used successfully to treat many chronic pain conditions. Unfortunately, few controlled trials have assessed which individuals benefit from long-term opioid therapy, and there is concern about the use of long-term opioid therapy in individuals with a substance-abuse history. This article contains three sections relevant to the assessment of individuals with chronic pain and a substance-abuse history who are receiving long-term opioid therapy. The first reviews the literature on opioid therapy, with a critique of biologic and environmental susceptibility factors for addiction. The second briefly reviews uncontrolled and controlled trials of opioid therapy for pain. The third reviews areas critical in assessing treatment efficacy and substance abuse in patients with chronic pain, both in terms of documentation of past behaviors and as a measure of outcome of opioid therapy. Potential guidelines for use of opioids in patients with chronic noncancer pain are outlined. Finally, questions are posed for future investigations of the efficacy of opioid therapy for patients with chronic pain and a substance-abuse history.