Human health depends on an adequate food supply, and food security depends on an adequate nitrogen (N) supply for crop production. But the balance between beneficial and harmful effects of N inputs used in crop production depends on the spatial scale in question. At a local level (or even a regional or national level), it is possible to meet food requirements with minimal exogenous N inputs to agriculture and tight N cycling where there is ample arable land and low population density dependent on local agriculture, or if the local population is wealthy enough to afford food imports. At a global scale, however, food security depends on producing an adequate food supply with finite amounts of arable land and water resources in a sustainable manner, which places constraints on N management options. Recent trends in global yields of staple food crops and trends in crop area indicate a trajectory towards food scarcity unless cultivated area expands substantially at the expense of natural ecosystems and marginal land, or the rate of crop yield increase is accelerated above historical trend lines. The preferred scenario is one of accelerated yield advance with little or no expansion of crop land to ensure protection of natural resources and biodiversity while meeting human food needs. But controlling the fate of N inputs in high-yield cropping systems is difficult. Sophisticated N management will be a cornerstone of the “ecological intensification” that will be needed in crop and livestock agriculture. Options for N management under an ecological intensification scenario will be explored in relation to large-scale commercial agriculture in developed countries and small-scale farming in developing countries, and for “organic” and “conventional” N management approaches. The goal is to ensure food security and protect environmental quality to avoid negative effects on human health.