Intrawound antibiotics have been used in orthopaedic surgery procedures to prevent the development of surgical site infections. Local delivery of antibiotic powder has demonstrated a notable reduction in surgical site infection in rabbit and rodent in vivo models, as well as in other surgical fields, including vascular, colorectal, cardiothoracic, and dermatologic surgery. Intrawound antibiotic powder has been used in many orthopaedic applications, including spine surgery, total joint arthroplasty, trauma, foot and ankle reconstruction, and elbow surgery. Although the theory behind the use of intrawound antibiotic powder is promising, it has potential adverse effects, including antibiotic resistance, circulatory collapse, and decreased bone healing. In addition, most studies in the orthopaedic literature on the use of intrawound antibiotic powder are retrospective in nature.