Aeromonas salmonicida is an age-old fish pathogen widely distributed in seawater and freshwater environments that causes significant economic losses to the global aquaculture industry. Genetic mutations and the emergence of thermophilic strains are factors in the continuous expansion of A. salmonicida’s host range. Beyond infecting fish, A. salmonicida poses a potential threat to mammalian and human health. This review synthesizes recent global research advances concerning A. salmonicida, encompassing strain characteristics, genomic features, virulence factors, and pathogenic mechanisms, as well as the clinical manifestations in infected fish and mammals, and discusses prevention and treatment methods. Particular emphasis is placed on evaluating the potential prophylactic roles of Chinese herbs and bacteriophages against A. salmonicida infection. Furthermore, the review provides perspectives on future research directions, diagnostics, and disease management, informed by contemporary domestic and international studies on this pathogen.