Human Salmonella infections are common; most infections are self-limiting, however severe disease may occur. Antimicrobial agents, while not essential for the treatment of Salmonella gastroenteritis, are essential for the treatment of thousands of patients each year with invasive infections. Fluoroquinolones and third-generation cephalosporins are the drugs-of-choice for invasive Salmonella infections in humans; alternative antimicrobial choices are limited by increasing antimicrobial resistance, limited efficacy, and less desirable pharmacodynamic properties. Antimicrobial-resistant Salmonella results from the use of antimicrobial agents in food animals, and these antimicrobial resistant Salmonella are subsequently transmitted to humans, usually through the food supply. The antimicrobial resistance patterns of isolates collected from persons with Salmonella infections show more resistance to antimicrobial agents used in agriculture than to antimicrobial agents used for the treatment of Salmonella infections in humans. Because of the adverse health consequences in humans and animals associated with the increasing prevalence of antimicrobial-resistant Salmonella, there is an urgent need to emphasize non-antimicrobial infection control strategies, such as improved sanitation and hygiene, to develop guidelines for the prudent usage of antimicrobial agents, and establishment of adequate public health safeguards to minimize the development and dissemination of antimicrobial resistance and dissemination of Salmonella resistant to these agents.