Readily available household chemicals, such as bleach, detergents, or cleaners, have the potential to interfere with urine drug tests. Since screening immunoassays are often the first line of testing, they are the most susceptible to adulteration due to these reagents’ potential to inhibit the interaction between the drug of interest and anti-drug antibodies, but definitive testing methods can also be affected. Immunoassays that detect 11-nor-9-carboxy-∆9 (THC-COOH) are often the most vulnerable to false negatives from adulterants. Adulterants which chemically modify the drug of interest (e.g., oxidation or degradation) may cause false negatives in both immunoassays and tandem liquid chromatography (LC) or gas chromatography (GC) mass spectrometry (MS) methods, as these changes may alter the drug’s column retention time and/or multiple reaction monitoring (MRM) profile. With the improved availability of specimen validity testing cassettes for automated chemistry analyzers and point-of-care adulterant strips from a variety of manufacturers, it is now easier than ever to quickly determine the presence of specimen tampering. However, the susceptibility of an assay to adulteration depends on its methodology, the drug of interest being measured, and the adulterant added. Therefore, careful selection of specimen validity tests and verifying specimen integrity prior to testing helps reduce the financial burden on the laboratory by minimizing time spent on invalid tests and enhances the accuracy and reliability of reported results for correct patient interpretations.