Despite progress in human gene discovery, we believe that regulations regarding subject protections have not fully kept pace. We believe that weaknesses in the current regulatory system include variations in the understanding of genetic principles and in the application of regulations. We discuss what our thoughts regarding steps needed to create an environment where information is gathered from all parties involved, including via research into many of the remaining questions, in order to ensure that research participant protection is adequate, appropriate and is an evolving process which will allow it to keep pace with the rapid advances in human genetics.