It is not surprising that humans have profoundly altered the global nitrogen (N) cycle in an effort to feed 7 billion people, because nitrogen is an essential plant and animal nutrient. Food and energy production from agriculture, combined with industrial and energy sources, have more than doubled the amount of reactive nitrogen circulating annually on land. Humanity has disrupted the nitrogen cycle even more than the carbon (C) cycle. We present new research results showing widespread effects on ecosystems, biodiversity, human health, and climate, suggesting that in spite of decades of research quantifying the negative consequences of too much available nitrogen in the biosphere, solutions remain elusive. There have been important successes in reducing nitrogen emissions to the atmosphere and this has improved air quality. Effective solutions for reducing nitrogen losses from agriculture have also been identified, although political and economic impediments to their adoption remain. Here, we focus on the major sources of reactive nitrogen for the United States (U.S.), their impacts, and potential mitigation options. Sources: ??? Intensive development of agriculture, industry, and transportation has profoundly altered the U.S. nitrogen cycle. ??? Nitrogen emissions from the energy and transportation sectors are declining, but agricultural emissions are increasing. ??? Approximately half of all nitrogen applied to boost agricultural production escapes its intended use and is lost to the environment. Impacts: ??? Two-thirds of U.S. coastal systems are moderately to severely impaired due to nutrient loading; there are now approximately 300 hypoxic (low oxygen) zones along the U.S. coastline and the number is growing. One third of U.S. streams and two fifths of U.S. lakes are impaired by high nitrogen concentrations. ??? Air pollution continues to reduce biodiversity. A nation-wide assessment has documented losses of nitrogen-sensitive native species in favor of exotic, invasive species. ??? More than 1.5 million Americans drink well water contaminated with too much (or close to too much) nitrate (a regulated drinking water pollutant), potentially placing them at increased risk of birth defects and cancer. More research is needed to deepen understanding of these health risks. ??? Several pathogenic infections, including coral diseases, bird die-offs, fish diseases, and human diarrheal diseases and vector-borne infections are associated with nutrient losses from agriculture and from sewage entering ecosystems. ??? Nitrogen is intimately linked with the carbon cycle and has both warming and cooling effects on the climate. Mitigation Options: ??? Regulation of nitrogen oxide (NOX) emissions from energy and transportation sectors has greatly improved air quality, especially in the eastern U.S. Nitrogen oxide is expected to decline further as stronger regulations take effect, but ammonia remains mostly unregulated and is expected to increase unless better controls on ammonia emissions from livestock operations are implemented. ??? Nitrogen loss from farm and livestock operations can be reduced 30-50% using current practices and technologies and up to 70-90% with innovative applications of existing methods. Current U.S. agricultural policies and support systems, as well as declining investments in agricultural extension, impede the adoption of these practices. Society faces profound challenges to meet demands for food, fiber, and fuel while minimizing unintended environmental and human health impacts. While our ability to quantify transfers of nitrogen across land, water, and air has improved since the first publication of this series in 1997, an even bigger challenge remains: using the science for effective management policies that reduce climate change, improve water quality, and protect human and environmental health. ?? The Ecological Society of America.