Chloride (Cl − ) has traditionally been considered harmful to agriculture because of its toxic effects in saline soils and its antagonistic interaction with nitrate (NO 3 − ), which impairs NO 3 − nutrition. It has been largely believed that Cl − antagonizes NO 3 − uptake and accumulation in higher plants, reducing crop yield. However, we have recently uncovered that Cl − has new beneficial macronutrient functions that improve plant growth, tissue water balance, plant water relations, photosynthetic performance, and water-use efficiency. The increased plant biomass indicates in turn that Cl − may also improve nitrogen use efficiency (NUE). Considering that N availability is a bottleneck for the growth of land plants excessive NO 3 − fertilization frequently used in agriculture becomes a major environmental concern worldwide, causing excessive leaf NO 3 − accumulation in crops such as vegetables, which poses a potential risk to human health. New farming practices aimed to enhance plant NUE by reducing NO 3 − fertilization should promote a healthier and more sustainable agriculture. Given the strong interaction between Cl − and NO 3 − homeostasis in plants, we have verified if indeed Cl − affects NO 3 − accumulation and NUE in plants. For the first time to our knowledge, we provide a direct demonstration which shows that Cl − , contrary to impairing NO 3 − nutrition, facilitates NO 3 − utilization and improves NUE in plants. This is largely due to Cl − improvement of the N-NO 3 − utilization efficiency (NU T E), having little or moderate effect on N-NO 3 − uptake efficiency (NU P E) when NO 3 − is used as the sole N source. Clear positive correlations between leaf Cl − content vs. NUE/NU T E or plant growth have been established at both intra-and interspecies levels. Optimal NO 3 − vs. Cl − ratios become a useful tool to increase crop yield and quality, agricultural sustainability and to reduce the negative ecological impact of NO 3 − on the environment and on human health.