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Salmonella spp are etiological agents of diarrhea and systemic infections in humans, most commonly as secondary contaminants of food originating from animals and the environment or irrigated by faecal wastes. Decades of indiscriminate use and abuse of antibiotics have resulted in increased development of antibiotic resistance in Salmonella spp to different antibiotics, creating major problems in treatment of relapsing salmonellosis and other enteric diseases across many age groups. This review x-rays the mechanisms of antibiotic resistances, genetic variations and clinical implications of antibiotic resistant Salmonella spp. The findings of this review revealed that antibiotic resistance in Salmonella spp resulted from a wide range of mechanisms developed by serovars of Salmonella. It has also been discovered from scientific studies that the multiple antibiotic resistances noticed in many serovars of Salmonella were due to genetic modifications in these serovars, chiefly mutation. Adequate drug use control and antibiotic combination therapies are encouraged for effective prophylaxis of relapsing salmonellosis caused by antibiotic resistant Salmonella spp.