The principles of antimicrobial management for head and neck infections include establishing an accurate clinical and microbiologic diagnosis and treating the patient initially with an empiric antimicrobial regimen based on predicted likelihood of success and reduced potential for resistance. Subsequent adjustments may be required based on clinical response and available culture results. This article summarizes the aerobic and anaerobic microbiology of selected acute and chronic infections of the head and neck and the approaches to antimicrobial therapy.