Background Antibiotic prophylaxis is an important component of dermatologic surgery, and recommendations in this area should reflect the updated 2007 guidelines of the American Heart Association, the American Dental Association with the American Academy of Orthopaedic Surgeons guidelines, and recent prospective studies on surgical site infection. Objective To provide an update on the indications for antibiotic prophylaxis in dermatologic surgery for the prevention of infective endocarditis, hematogenous total joint infection, and surgical site infection. Methods A literature review was performed, expert consensus was obtained, and updated recommendations were created, consistent with the most current authoritative guidelines from the American Heart Association and the American Dental Association with the American Academy of Orthopaedic Surgeons. Results For patients with high-risk cardiac conditions, and a defined group of patients with prosthetic joints at high risk for hematogenous total joint infection, prophylactic antibiotics are recommended when the surgical site is infected or when the procedure involves breach of the oral mucosa. For the prevention of surgical site infections, antibiotics may be indicated for procedures on the lower extremities or groin, for wedge excisions of the lip and ear, skin flaps on the nose, skin grafts, and for patients with extensive inflammatory skin disease. Limitations These recommendations are not based on multiple, large-scale, prospective trials. Conclusions There is a strong shift away from administration of prophylactic antibiotics in many dermatologic surgery settings, based on updated authoritative guidelines. These recommendations provide guidance to comply with the most current guidelines, modified to address dermatology-specific considerations. Managing physicians may utilize these guidelines while individualizing their approach based on all clinical considerations.