Treatment guidelines for chronic noncancer pain recommend opioids for carefully selected, closely monitored patients. However, many primary care physicians have a limited understanding of urine toxicology testing, which is the standard for monitoring opioid therapy. This article describes the technical aspects of urine toxicology testing and provides recommendations for monitoring patients to maximize the safety of opioid therapy. Articles were identified in PubMed, Medline, and EMBASE (January 1980-November 2008) using the search term opioid in combination with the terms urine toxicology, compliance monitoring, abuse, and diversion. Articles characterizing the pharmacology of individual opioids and practice guidelines for the management of chronic pain were also identified. Articles selected for inclusion discussed technical aspects of urine toxicology testing, clinical aspects of monitoring, and issues related to abuse and diversion. Urine tests can detect prescribed and illicit substances that are present above a specific threshold, but they provide limited data about the source, dose, or route of administration of substances detected. Effective monitoring requires careful test selection, an understanding of pharmacologic and metabolic factors influencing test results, and awareness of methods by which patients who are substance abusers may tamper with test specimens to escape detection. All patients prescribed opioids, not just those considered at risk for abuse, should undergo urine toxicology testing. Given its inherent complexities, effective urine testing requires close collaboration between the primary care physician and a reliable laboratory to develop an appropriate test protocol for each patient and to interpret test results.