Abstract: Salmonella is a bacterial pathogen with significant morbidity and mortality in humans driven by environmental and socioeconomic factors. As the third leading cause of death in humans among diarrheal diseases, Salmonella is a major public health threat which demands integrated interventions. The pathogenicity, determinants, prevention, control, and treatment of MDR Salmonella infections were reviewed following a literature search on PubMed and Google Scholar which yielded 405 articles, of which 79 articles were selected after screening. Enteric fevers caused by typhoidal Salmonella serotypes - S. Typhi, S. Paratyphi A, S. Paratyphi B, and S. Paratyphi C are found only in humans in mostly developing countries, while food poisoning and gastroenteritis caused by NTS serotypes - S. Typhimurium and S. Enteritidis respectively found in humans and animals in developing and developed countries accounts for 70% of Salmonella infections in humans associated with eating contaminated food products of poultry origin and also causes iNTS disease in humans. Preventing Salmonella contamination of animal products, water, vegetables and fruits, and promoting the safety and quality of foods for human and animal consumption is achievable through food and water hygiene, personal and environmental hygiene, biosecurity, preservation of animal feeds, food safety and HACCP principles, and epidemiological surveillance. Salmonella infection is basically treated using antibiotics, however, the rise in MDR strains has resulted in treatment with antibiotic-alternatives including probiotics, prebiotics, and vaccines. Further research is recommended in treating iNTS disease, developing human vaccine against NTS, and using bacteriophages, antimicrobial peptides, organic acids, and essential oils as antibiotic-alternatives.