A common application of drug testing for clinical purposes is to assess adherence to controlled substances that are prescribed for long-term use, a practice particularly common for opioids. Testing can help to identify aberrant drug behaviors and may help promote and improve patient education and safety. Considerations when selecting the approach to adherence testing include assuring that the drugs of interest are detected at appropriate cutoff concentrations for the population being tested, an understanding of test limitations, and risks of specimen adulteration. Laboratories may provide tools to guide interpretation, particularly when results (positive and/or negative) are unexpected. Regardless, consulting the testing laboratory regarding the investigation of unexpected results is recommended.