NIOSH has been at the forefront of research on engineered nanomaterials since the early 2000’s. As the NIOSH Nanotechnology Research Center (NTRC) celebrates its 20th anniversary, we look back over two decades of NIOSH NTRC published guidance to help reduce worker exposures to engineered nanomaterials (ENMs). Both companies and workers use this guidance to keep workers safer. NTRC research has led to improved recommendations for controlling exposures during advanced manufacturing processes. Organizations have also used our guidance to base global standards. Here, we reflect on how our guidance and publications have evolved through decades of research. We also discuss the needs for future research efforts.