This chapter focuses predominantly on staphylococcal food poisoning (SFP), another toxin-mediated illness. SFP, also known as staphylococcal gastroenteritis, is not an infection but is a foodborne intoxication caused by one or more staphylococcal enterotoxins (SEs). It appears to have been initially reported in 1894 as a family outbreak due to undercooked meat from a sick cow that became contaminated with Staphylococcus aureus. Staphylococci are often divided into coagulasepositive staphylococci and coagulase-negative staphylococci (CNS), on the basis of coagulase production or the presence of a coagulase gene. Staphylococcal osmotolerance is problematic for food safety since blocked growth of competing bacteria can result in a more likely overgrowth of S. aureus. Staphylococci are ubiquitous in air, dust, sewage, water, milk, and many foods and on food equipment, environmental surfaces, humans, and animals. SE production is affected by temperature, pH, and osmotic conditions and is also regulated at the molecular level. The oligonucleotideoligosaccharide- binding fold containing a β-barrel structure capped with an α-helix comprises much of one domain and is present in other toxins including cholera toxin, pertussis toxin, and Shiga toxin. Recent studies demonstrated that staphylococcal pathogenicity island (SaPI) is mobilized by staphylococcal bacteriophages and endogenous prophages, suggesting that SE genes might be transferred horizontally. The identification of novel toxins and improved methods of detection have also indicated that SE production is much more widespread than originally thought and includes species of staphylococci other than S. aureus.