One of the ‘grand challenges’ of this age is the anthropogenic impact exerted on the nitrogen cycle. Issues of concern range from an excess of fixed nitrogen resulting in environmental pressures for some regions, while for other regions insufficient fixed nitrogen affects food security and may lead to health risks. To address these issues, nitrogen needs to be managed in an integrated fashion, at a variety of scales (from global to local). Such management has to be based on a thorough understanding of the sources of reactive nitrogen released into the environment, its deposition and effects. This requires a comprehensive assessment of the key drivers of changes in the nitrogen cycle both spatially, at the field, regional and global scale and over time. In this focus issue, we address the challenges of managing reactive nitrogen in the context of food production and its impacts on human and ecosystem health. In addition, we discuss the scope for and design of management approaches in regions with too much and too little nitrogen. This focus issue includes several contributions from authors who participated at the N2013 conference in Kampala in November 2013, where delegates compiled and agreed upon the ‘Kampala Statement-for-Action on Reactive Nitrogen in Africa and Globally’. These contributions further underline scientifically the claims of the ‘Kampala Statement’, that simultaneously reducing pollution and increasing nitrogen available in the food system, by improved nitrogen management offers win-wins for environment, health and food security in both developing and developed economies. The specific messages conveyed in the Kampala Statement focus on improving nitrogen management (I), including the reduction of nitrogen losses from agriculture, industry, transport and energy sectors, as well as improving waste treatment and informing individuals and institutions (II). Highlighting the need for innovation and increased awareness among stakeholders (III) and the identification of policy and technology solutions to tackle global nitrogen management issues (IV), this will enable countries to fulfil their regional and global commitments.