Although newborn screening (NBS) for inborn errors of metabolism has been successfully utilized in the US for decades, only recently has this screening program expanded to include disorders of immunity. Severe combined immunodeficiency (SCID) became the first disorder of immunity to be screened on a population wide basis in 2008. While NBS for SCID has been successful, the implementation of population-based screening programs is not without controversy, and there remain barriers to the nationwide implementation of this test. In addition, as the program has progressed we have learned of new challenges in the management of newborns that fail this screen.