Since the beginning of newborn screening for metabolic and other disorders in 1964, advances in the understanding of the disorders identified and development of new methods of testing newborn screening blood spots have contributed to improved health in children. Pediatricians and others involved in the health care of infants must be able to participate in the assessment and confirmatory testing of infants who have an abnormal test result and in the care of infants identified with a disorder. Expansion in the technology and number of disorders identified has complicated this process. As more and a greater variety of disorders are tested for and identified, a crucial collaborative role has emerged for the newborn screening programs and their public health professionals, the tertiary care specialists in the disorders and the primary care clinicians who comprise the medical home of the infants identified. This collaboration needs to provide prompt results of the newborn screening tests, expeditious and expert confirmatory testing and an effective care plan for the affected infant to realize the benefits of treatment for children with otherwise devastating disorders.