Opioids are important, if not essential, agents in treating certain types of chronic pain. However, the prevalence of drug misuse, abuse, and addiction has fostered considerable consternation among physicians, who may hesitate to prescribe these medications both due to concern for patients (misuse, abuse, and addiction), and fears of prosecution and/or professional sanction. Such practice may reflect 1) inadequate knowledge about patients' susceptibility to, or current drug misuse or abuse; 2) lack of familiarity with extant assessments and/or regulations, and/or 3) an unanticipated reaction to existing guidelines, policies or laws. We posit that assessing patients' predisposition to, and patterns of, drug misuse/abuse is a vital first step toward establishing and maintaining the safe and effective use of opioid analgesics in the treatment of chronic pain. Adherence monitoring is critical to identify patients' prior and current drug use, establish treatment basis, and evaluate compliance, so as to avoid misuse and abuse, and ensure sound and proper pain management. This paper provides a review of the numerous monitoring approaches that have been described in the literature and addresses the benefits and limitations of these techniques and tools. The complex nature of the problem of drug misuse and abuse is discussed, and while no single monitoring technique can fully address this complex issue, we describe how multiple approaches to adherence monitoring may be employed to sustain the prudent use of opioids for the treatment of chronic pain.