This document represents the U.S. government’s commitment to steer future research advancements in nanotechnology, aligning with the needs of the economy and society. It updates the 2011 NNI NanoEHS Research Strategy and assesses progress in six core research areas; describes cross-cutting themes in the environmental, health, and safety implications of nanotechnology; and identifies strategic actions that the NNI community should consider for the advancement of nanotechnology research.