A core goal of both US and European pollution control policies has been to establish rules and regulations pertaining to the movement of reactive-nitrogen (Nr) through the environment. This is manifest in US federal legislation such as the Clean Air Act Amendments and the Clean Water Act Amendments and in various protocols of the United Nations Economic Commission for Europe (UNECE) and its Convention on Long-Range Transboundary Air Pollution (CLRTAP). In this paper, we begin by reviewing the two US laws and their effectiveness and make some comparisons with the approaches used mainly in Europe by the UNECE and CLRTAP. Next we use the Mississippi drainage/Gulf of Mexico hypoxia case study to highlight the importance of applying a "systems approach" to address the reactive nitrogen problem at the regional scale. After briefly posing a number of unanswered questions related to nitrogen control policies, we conclude by sketching a blueprint for future actions related to the development of improved policies to regulate reactive nitrogen.