AUTHOR=Udvardi Michael , Below Frederick E. , Castellano Michael J. , Eagle Alison J. , Giller Ken E. , Ladha Jagdish Kumar , Liu Xuejun , Maaz Tai McClellan , Nova-Franco Barbara , Raghuram Nandula , Robertson G. Philip , Roy Sonali , Saha Malay , Schmidt Susanne , Tegeder Mechthild , York Larry M. , Peters John W. TITLE=A Research Road Map for Responsible Use of Agricultural Nitrogen JOURNAL=Frontiers in Sustainable Food Systems VOLUME=Volume 5 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/sustainable-food-systems/articles/10.3389/fsufs.2021.660155 DOI=10.3389/fsufs.2021.660155 ISSN=2571-581X ABSTRACT=Nitrogen (N) is an essential but generally limiting nutrient for biological systems. Development of the Haber-Bosch industrial process for ammonia synthesis helped to relieve N-limitation of agricultural production, fueling the Green Revolution and reducing hunger. However, the massive use of industrial N-fertilizer has doubled the global N-cycle with dramatic environmental consequences that threaten planetary health. Consequently, there is an urgent need to reduce losses of reactive-N from agriculture, while ensuring sufficient N-inputs for food security. Here, we review current knowledge related to nitrogen use efficiency (NUE) in agriculture and identify research opportunities in the areas of agronomy, plant breeding, biological nitrogen fixation (BNF), soil N-cycling, and modeling to achieve responsible, sustainable use of N in agriculture. Amongst these opportunities, improved agricultural practices that synchronize crop N-demand with soil N-availability are low-hanging fruit. Crop breeding that targets root and shoot physiological processes will likely increase N uptake and utilization of soil N, while breeding for BNF effectiveness in legumes will enhance overall system NUE. Likewise, engineering of novel nitrogen-fixing symbioses in non-legumes could reduce the need for chemical fertilizers in agroecosystems. The use of simulation modeling to conceptualize the complex, interwoven processes that affect agroecosystem NUE, along with multi-objective optimization, will also accelerate NUE gains.