Foodborne illnesses cause a substantial human and financial burden. Despite sanitary infrastructure improvements, the incidence of foodborne bacterial infections due to non-typhoidal salmonellae (NTS), Campylobacter jejuni, and enterohemorrhagic Escherichia coli (EHEC) has risen over the last two decades. Overall, viruses account for two thirds of all foodborne illness. Most foodborne illnesses are self-limited. Supportive therapy with rehydration and the correction of electrolyte abnormalities is usually sufficient. Antibiotics play a beneficial role in the treatment of patients with certain foodborne diseases, such as listeriosis and typhoid fever, and all patients with tissue invasive or bloodstream infections. Immunocompromised patients should be treated presumptively. Antibiotics are of variable efficacy for the treatment of many infections limited to the gastrointestinal tract, and recommendations differ between pathogens. Antibiotics are generally helpful for shigellosis and cholera, and possibly beneficial for campylobacteriosis. However, antibiotics are potentially harmful in uncomplicated NTS and EHEC gastroenteritis and generally should not be used. Toxin-mediated food poisoning usually does not require specific therapy. The exception is botulism, for which botulinum antitoxin is highly efficacious if used early in the course of illness. Empiric therapy for gastroenteritis is possibly beneficial, though the magnitude of benefit is modest and incurs the risk of inadvertently treating NTS or EHEC. The choice of antibiotic should be based on local resistance patterns and the results of susceptibility testing.