The National Human Genome Research Institute, in close collaboration with its research community, is pursuing an ambitious research agenda to facilitate and promote the implementation of genomics in clinical care. Since 2011, research programs utilizing next-generation sequencing in the management of cancer and other multigenic conditions, workup of undiagnosed conditions, and evaluation of disorders of the newborn period have been initiated, along with projects identifying clinically actionable variants and exploring the ethical and social implications of reporting these findings. Several genomic medicine symposia and other consultations have helped to shape these research initiatives and develop educational materials for physicians and others working to implement the use of genomic findings in clinical care. These efforts provide a valuable complement to the highly successful basic genomics research enterprise that has at last enabled the transition of genomics from the bench to the bedside. © 2014 Wiley Periodicals, Inc.