Drug testing in newborns comes with analytical, therapeutic, and legal issues, and interpretation of results may be left to physicians, nurses, or social services workers. The unique analytical and legal caveats pose a variety of challenges and therapeutic issues. Positive drug screening results can allow for proper medical management of withdrawal symptoms for certain drug classes. Legal implications and involvement of social services for assessment of child safety surround positive urine or meconium drug samples. Because laboratory results can potentially remove newborns from their biological parents, the caveats and limitations of drug testing in this population are of utmost importance.