Food production and power generation have increased to feed growing populations and to keep pace with economic development, leading to major human alteration of the global nitrogen (N) cycle. The result is a global challenge, with many regions having ‘too much’ or ‘too little’ nitrogen. As di-nitrogen (N2) in the atmosphere, nitrogen is one of the most abundant elements, but which cannot be used by most organisms. Conversely, reactive nitrogen (Nr) is essential for organisms, but is mostly in short supply for natural ecosystems. Human activities have polarized the differences in Nr flows between different world regions, leading to major sustainability challenges, with implications for food security, adverse impacts on health and ecosystems, and the need to develop tools and policies for better management. In developed regions, abundant use of manufactured fertilizers, crop biological nitrogen fixation and inadvertent formation of nitrogen oxides via combustion processes are leading to a plethora of environmental problems. These threaten air quality, water quality, soil quality, greenhouse gas balance, stratospheric ozone levels, biodiversity and human health. At the same time, in many developing regions, insufficient access to reactive nitrogen is leading to degradation of agricultural soils including N depletion, making it vital to reduce losses and recycle available nitrogen stocks. Nitrogen emissions as a result of agricultural practices and combustion for energy represent a major economic loss. Adding up all N losses in the world (excluding emissions from oceans) amounts to a lost agricultural fertilizer resource worth around $200 billion USD annually. The societal costs to human health, ecosystems and climate are even larger at $400–4000 billion USD annually. Knowledge of these figures can help motivate society to optimize with ‘just enough’ nitrogen. This chapter provides an overview of results from the 6th International Nitrogen Conference, Kampala (Uganda), which considered the question of how to optimize practices for ‘just enough’ nitrogen both internationally and specifically for the African Continent. From experimental trials to scenario analysis, the contributions demonstrate the approaches being used. The messages in very different regions often turn out to be surprisingly similar. They encompass all aspects of society: optimizing the use of available fertilizer and manure resources (both under excess and under scarcity conditions), improving nitrogen use efficiency, developing landscape integration, and optimizing our food choices by prior planning that can also reduce food waste. Together, such nitrogen-related strategies will have major benefits for global environmental sustainability.