Nitrogen (N) is an essential mineral nutrient for plant growth and development. N deficiency is the major factor limiting plant growth and crop production in most natural and agricultural soils. The green revolution of the 1960's boosted crop yields through cultivation of semi-dwarf plant varieties. However, green revolution wheat and rice varieties have relatively poor nitrogen use efficiency (NUE), require a high N fertilizer supply to achieve maximum yield potential, and this leads to an increase in production costs and environmental problem. Therefore, a major challenge for sustainable agriculture is whether improvement of NUE through the reduction of N fertilizer supply can be achieved without yield penalty. In this review, we summarize the recent advances in understanding of molecular mechanisms underlying the regulation of N-responsive plant growth, utilization and possibility for improvements of NUE in crops, and new breeding strategies through modulation of N-responsive growth-metabolism coordination for future sustainable agriculture.