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AbstractAeromonasspecies (spp.) are well-known fish pathogens, several of which have been recognized as emerging human pathogens. The organism is capable of causing a wide spectrum of diseases in humans, ranging from gastroenteritis, wound infections, and septicemia to devastating necrotizing fasciitis. The systemic form of infection is often fatal, particularly in patients with underlying chronic diseases. Indeed, recent trends demonstrate rising numbers of hospital-acquiredAeromonasinfections, especially in immuno-compromised individuals. Additionally,Aeromonas-associated antibiotic resistance is an increasing challenge in combating both fish and human infections. The acquisition of antibiotic resistance is related toAeromonas’ innate transformative properties including its ability to share plasmids and integron-related gene cassettes between species and with the environment. As a result, alternatives to antibiotic treatments are desperately needed. In that vein, many treatments have been proposed and studied extensively in the fish-farming industry, including treatments that targetAeromonasquorum sensing. In this review, we discuss current strategies targeting quorum sensing inhibition and propose that such studies empower the development of novel chemotherapeutic approaches to combat drug-resistantAeromonasspp. infections in humans. Key points• Aeromonas notoriously acquires and maintains antimicrobial resistance, making treatment options limited.• Quorum sensing is an essential virulence mechanism in Aeromonas infections.• Inhibiting quorum sensing can be an effective strategy in combating Aeromonas infections in animals and humans.