Newborn screening is performed under public health authority, with analysis carried out primarily by public health laboratories or other centralized laboratories. Increasingly, opportunities to improve infant health will arise from including screening tests that are completed at the birth centers instead of in centralized laboratories, constituting a significant shift for newborn screening. This report summarizes a framework developed by the US Secretary of Health and Human Services Advisory Committee on Heritable Disorders in Newborns and Children based on a series of meetings held during 2011 and 2012. These meetings were for the purpose of evaluating whether conditions identifiable through point-of-care screening should be added to the recommended universal screening panel, and to identify key considerations for birth hospitals, public health agencies, and clinicians when point-of-care newborn screening is implemented.