The appropriate use of antibiotic prophylaxis is confusing for all surgeons and it is certainly not straight-forward for dermatologists. There are no set guidelines which encompass skin surgery. This article reviews antibiotic prophylaxis both to prevent wound infections and to prevent endocarditis. Some of the issues and controversies surrounding the use of antibiotic prophylaxis are discussed, and guidelines are provided which should be of assistance to those who perform dermatologic surgery.