The inaugural RUSP Roundtable in August 2015 convened 30 newborn screening (NBS) opinion leaders from academia, governmental agencies, clinical and social research, public health, private industry, and patient advocacy in a unique, open, independent forum to speak with candor about current newborn screening challenges, concerns, and developments with an eye toward the future of NBS. The discussion started with the RUSP criteria but quickly broadened to include a multitude of NBS issues.