Surgical site infection (SSI) is one of the most common complications of surgery in both adults and children. The purpose of the present review is to highlight the progress in the understanding of SSIs and the current role of antimicrobial prophylaxis (AMP).An SSI is diagnosed by a constellation of clinical findings occurring within 30 days of surgery. Pathologic organisms responsible for the development of an SSI are mainly limited to Gram-positive bacteria. Two well documented risk factors for the development of SSI in children are wound classification by the Centers for Disease Control (CDC) and procedure duration. Administration of appropriate AMP prior to skin incision has been shown to reduce the incidence of SSI in selected procedures. However, there is a lack of consensus on which procedures in children require AMP.Improvement in the perioperative care of children has reduced both the incidence and outcomes of SSI. However, several controversies still exist in the use of AMP in children. Future work by pediatricians, pediatric surgeons, and pediatric infectious disease specialists will enable us to better understand the specific indications and appropriate AMP in children.