On March 10-11, 2016, the National Academies of Sciences, Engineering, and Medicine held a public symposium on potential U.S. government policies for the oversight of gain-of- function (GOF) research. This was the Academies’ second meeting held at the request of the U.S. government to provide a mechanism to engage the life sciences community and the broader public and solicit feedback on optimal approaches to ensure effective federal oversight of GOF research as part of a broader U.S. government deliberative process. The first symposium, held in December 2014, examined the underlying scientific and technical questions surrounding the potential risks and benefits of GOF research involving pathogens with pandemic potential. The second symposium focused on discussion of the draft recommendations regarding GOF research of a Working Group of the National Science Advisory Board for Biosecurity. This report summarizes the key issues and ideas identified during the second symposium.