Junye Shen, Xin Yin, Yuheng Zhu, W. LI, Mabruk Adams, Bing-Jie Ni, Chongjun Chen
Anaerobic ammonium oxidation (anammox), as a breakthrough low-carbon nitrogen removal technology, is energy-efficient and cost-effective for treating high-ammonium, low C/N wastewaters. However, excessive concentrations of ammonium (NH4+) and nitrite (NO2−), especially in the form of free ammonia (FA) and free nitrous acid (FNA), exert strong biotoxic effects on anammox bacteria (AnAOB) and severely hinder the wide application of the anammox process. In this review, we comprehensively evaluate high-nitrogen inhibition in anammox systems, focusing on impacts on nitrogen removal performance and sludge properties. From molecular–cellular–ecological perspectives, this work systematically elucidates the inhibition and response mechanisms under high-nitrogen stress, covering membrane structure, key enzymes and functional genes, extracellular polymeric substances (EPS), and microbial community. In addition, we explore the roles of coexisting organics and microbial interactions in system-level responses. To mitigate high-nitrogen inhibition, a series of effective recovery strategies are summarized, including biomass intervention management, process parameter optimization, and exogenous additive supplementation. Finally, we propose biological enhancement measures based on the enrichment of Ca. Kuenenia to improve anammox tolerance. This review bridges microbial insights and engineering applications to advance the broader implementation of anammox-based systems in full-scale wastewater treatment.