Resumen: The aims of this chapter are: (i) First, to present new experimental evidenceshowingthe signal-role of nitrate in the correction and improvement of the deleterious effects of ammonium-and/or urea-based nutritionin different plant species, either dicotyledonous or monocotyledonous. Likewise, we discuss the different and complementary mechanisms, which are expressed at diverse but interconnected molecular and physiological levels, responsible for this specific role of nitrate. This discussion is accompanied by the propositionof different hypothesisthat could explain these experimental results and orientate future research in this important field as well. (ii) Second, we also discuss the different methodologies that might be developed in order to apply this basic researchin the development of new nitrogenfertilizerswith higher metabolic efficiency and lower potential environmental risks. (iii) Finally, we propose a framework for future research oriented to do a synthesis-involving and inter-connecting this basic and applied research -related to both the future development of nitrogen-related fertilizersand cropyield ¿quality improvement.