Crop productivity relies heavily on nitrogen (N) fertilization. Production and application of N fertilizers consume huge amounts of energy, and excess is detrimental to the environment; therefore, increasing plant N use efficiency (NUE) is essential for the development of sustainable agriculture. Plant NUE is inherently complex, as each step—including N uptake, translocation, assimilation, and remobilization—is governed by multiple interacting genetic and environmental factors. The limiting factors in plant metabolism for maximizing NUE are different at high and low N supplies, indicating great potential for improving the NUE of current cultivars, which were bred in well-fertilized soil. Decreasing environmental losses and increasing the productivity of crop-acquired N requires the coordination of carbohydrate and N metabolism to give high yields. Increasing both the grain and N harvest index to drive N acquisition and utilization are important approaches for breeding future high-NUE cultivars.