Abstract
Nitrogen (N) is the primary macronutrient that supports global agriculture. The Haber-Bosch process revolutionized the use of synthetic N fertilizers, enabling significant increases in crop yield. However, N losses from fertilization led to negative impacts on the environment. Improving crops' N use efficiency (NUE) has been constrained by the limited understanding of N uptake and assimilation mechanisms, and the role of plant-microbe interactions. Among biological approaches, N fixation by cover crops and rhizobia symbioses represents a cornerstone strategy for improving NUE. The adoption of plant growth-promoting bacteria and arbuscular mycorrhizal fungi may enhance N acquisition by increasing root surface, modulating phytohormone levels, and facilitating nutrient transfer. Advances in plant molecular biology have identified key players and regulators of NUE (enzymes, transporters, and N-responsive transcription factors), which enhance N uptake and assimilation. Emerging biotechnological strategies include de novo domestication by genome editing of crop wild relatives to combine NUE traits and stress resilience back into domesticated cultivars. Additionally, novel fertilizers with controlled nutrient release and microbe-mediated nutrient mobilization, hold promise for synchronizing N availability with plant demand, reducing losses, and increasing NUE. Together, these strategies form a multidimensional framework to enhance NUE, mitigate environmental impacts, and facilitate the transition towards more sustainable agricultural systems.