Humans continue to transform the global nitrogen cycle at a record pace, reflecting an increased combustion of fossil fuels, growing demand for nitrogen in agriculture and industry, and pervasive inefficiencies in its use. Much anthropogenic nitrogen is lost to air, water, and land to cause a cascade of environmental and human health problems. Simultaneously, food production in some parts of the world is nitrogen-deficient, highlighting inequities in the distribution of nitrogen-containing fertilizers. Optimizing the need for a key human resource while minimizing its negative consequences requires an integrated interdisciplinary approach and the development of strategies to decrease nitrogen-containing waste.