Clinicians often question negative toxicology results when patients clinically appear to have overdosed on a drug or had a toxic response to a pharmaceutical agent. Certain benzodiazepines, date rape drugs, gamma hydroxy butyric acid and ketamine as well as novel psychoactive substances, including bath salts and synthetic cannabinoids, may not be detected by routine toxicology analysis in a clinical laboratory. Academic medical centers and regional medical centers may have the capability to do further testing, but a smaller hospital laboratory may not have instrumentation for further analysis. This short course will emphasize how to effectively communicate with clinicians regarding which drug may be present so that the specimen can be tested further or sent to an outside laboratory. Moreover, an algorithm of further testing based on clinical symptoms will be presented.