AbstractNitrogen (N) is an essential macronutrient for plants and profoundly affects crop yields and qualities. Ammonium (NH4+) and nitrate (NO3−) are major inorganic N forms absorbed by plants from the surrounding environments. Intriguingly, NH4+ is usually toxic to plants when it serves as the sole or dominant N source. It is thus important for plants to coordinate the utilization of NH4+ and the alleviation of NH4+ toxicity. To fully decipher the molecular mechanisms underlying how plants minimize NH4+ toxicity may broadly benefit agricultural practice. In the current minireview, we attempt to discuss recent discoveries in the strategies for mitigating NH4+ toxicity in plants, which may provide potential solutions for improving the nitrogen use efficiency (NUE) and stress adaptions in crops.