The success of the Green Revolution largely relies on fertilizers, and a new Green Revolution is very much needed to use fertilizers more economically and efficiently, as well as with more environmental responsibility. The use efficiency of nitrogen, phosphorus, and potassium is controlled by complex gene networks that co-ordinate uptake, re-distribution, assimilation, and storage of these nutrients. Great progress has been made in breeding nutrient-efficient crops by molecularly engineering root traits desirable for efficient acquisition of nutrients from soil, transporters for uptake, redistribution and homeostasis of nutrients, and enzymes for efficient assimilation. Regulatory and transcription factors modulating these processes are also valuable in breeding crops with improved nutrient use efficiency and yield performance.