Immunoassay is used extensively for drug testing in pain management. Drug testing for the purpose of compliance monitoring is fundamentally different from forensic applications, which may rely on immunoassay screening to rapidly identify "negative" samples. In clinical settings, focus is shifted from identification of select drugs of abuse with low positivity rates to detection of a wide variety of licit and illicit compounds with expected high positivity rates. The primary drug classes of interest in this population, opioids and benzodiazepines, require special testing considerations when immunoassay is used. This review highlights the performance characteristics of immunoassay, with special emphasis on prescription drug classes and testing at the point-of-care.