Salmonellosis is a worldwide health problem; Salmonella infections are the second leading cause of bacterial foodborne illness in the United States. Approximately 95% of cases of human salmonellosis are associated with the consumption of contaminated products such as meat, poultry, eggs, milk, seafood, and fresh produce. Salmonella can cause a number of different disease syndromes including gastroenteritis, bacteremia, and typhoid fever, with the most common being gastroenteritis, which is often characterized by abdominal pain, nausea, vomiting, diarrhea, and headache. Typically the disease is self-limiting; however, with more severe manifestations such as bacteremia, antimicrobial therapy is often administered to treat the infection. Currently, there are over 2,500 identified serotypes of Salmonella. A smaller number of these serotypes are significantly associated with animal and human disease including Typhimurium, Enteritidis, Newport, Heidelberg, and Montevideo. Increasingly, isolates from these serotypes are being detected that demonstrate resistance to multiple antimicrobial agents, including third-generation cephalosporins, which are recommended for the treatment of severe infections. Many of the genes that encode resistance are located on transmissible elements such as plasmids that allow for potential transfer of resistance among strains. Plasmids are also known to harbor virulence factors that contribute to Salmonella pathogenicity. Several serotypes of medical importance, including Typhimurium, Enteritidis, Newport, Dublin, and Choleraesuis, are known to harbor virulence plasmids containing genes that code for fimbriae, serum resistance, and other factors. Additionally, many Salmonella contain pathogenicity islands scattered throughout their genomes that encode factors essential for bacterial adhesion, invasion, and infection. Salmonella have evolved several virulence and antimicrobial resistance mechanisms that allow for continued challenges to our public health infrastructure.