Human activity has had the single largest influence on the global nitrogen (N) cycle by introducing unprecedented amounts of reactive-N into ecosystems. A major portion of this reactive-N, applied as fertilizer to crops, leaks into the environment with cascading negative effects on ecosystem functions and contributes to global warming. Natural ecosystems use multiple pathways of the N-cycle to regulate the flow of this element. By contrast, the large amounts of N currently applied in agricultural systems cycle primarily through the nitrification process, a single inefficient route that allows much of the reactive-N to leak into the environment. The fact that present agricultural systems do not channel this reactive-N through alternate pathways is largely due to uncontrolled soil nitrifier activity, creating a rapid nitrifying soil environment. Regulating nitrification is therefore central to any strategy for improving nitrogen-use efficiency. Biological nitrification inhibition (BNI) is an active plant-mediated natural function, where nitrification inhibitors released from plant roots suppress soilnitrifying activity, thereby forcing N into other pathways. This review illustrates the presence of detection methods for variation in physiological regulation of BNI-function in field crops and pasture grasses and analyzes the potential for its genetic manipulation. We present a conceptual framework utilizing a BNIplatform that integrates diverse crop science disciplines with ecological principles. Sustainable agriculture will require development of production systems that include new crop cultivars capable of controlling nitrification (i.e., high BNIcapacity) and improved agronomic practices to minimize leakage of reactive-N during the N-cycle, a critical requirement for increasing food production while avoiding environmental damage.