In this review, the singularity of cropping systems under a Mediterranean climate is analyzed in their relationship with nitrogen management. The work includes original data analyzing 1) the evolution of the agri-food system of the countries of the Mediterranean basin (1961-2013); 2) the interaction between nitrogen and water through the comparison of irrigated and dryland cereal crops in a Mediterranean aridity gradient, 3) the main determinants that facilitate the emissions of N compounds in their difference with the temperate climate, 4) the connection with the adaptation of cropping systems to climate change; 5) the particularities of the Mediterranean basins in their relationship with nitrate pollution. All these results are analyzed from the perspective of contributing to agro-environmental policies adapted to the particularities of Mediterranean agriculture.