Infection rates in dermatologic surgery are low, ranging on average from 1 to 3%. Studies have shown that many practitioners likely overuse antibiotics, both for prevention of wound infection and in endocarditis prophylaxis. This article discusses patient and environmental risk factors in would infection. Data on wound infection prophylaxis are reviewed, and specific guidelines set forth with regards to appropriate antibiotic usage, drug selection, dosage, and timing. In addition, recommendations surrounding endocarditis and prosthetic joint infection prophylaxis are presented as they apply to dermatologic surgery.