Antibiotics have well-known benefits when prescribed appropriately. However, antibiotics are often misused, and giving them correctly is an integral part of good clinical practice. Important considerations when prescribing antibiotics across the surgical pathway include understanding the difference between surgical prophylaxis, empiric therapy, and targeted therapy. Administering antibiotics is integral to the daily work of surgeons. It is important that surgeons know the minimal requirements, such as the antibiotic spectrum of activity and effective drug dosing. Without these minimal requirements, surgeons will increase the likelihood of treatment failures and adverse effects, including the selection of opportunistic infections such as Clostridioides difficile infection and the development of antimicrobial resistance.