© 2017 American Society of Addiction Medicine. For patients who receive opioids or benzodiazepines, urine drug tests shed some light on the question of whether patients take their medicines as directed. How often do patients prescribed these drugs fall short? A commercial laboratory's review of 144,535 urine samples found a high prevalence of disagreement between what clinic staff reported on laboratory requisitions and what was detected in the urine. Before concluding that most patients fail to take opioids and benzodiazepines correctly, we should take into account that urine tests sent to national laboratories reflect a skewed subset of patients who receive prescriptions. Additionally, laboratory requisitions prepared by office staff are not likely to perfectly reflect what is prescribed. Nevertheless, this report by McClure et al reminds us that urine drug test results will frequently diverge from what clinicians expect. Urine tests convey a signal requiring interpretation followed by careful, patient-centered decisions.