Antibiotics are used in dentistry to treat an existing infection therapeutically or to prevent an infection prophylactically. To prevent a perioperative infection (primary prophylaxis), prophylactic antibiotics may be administered when a surgical device, such as a prosthetic cardiac valve, is placed. They also may be administered to patients who have an existing medical condition or have received a previously placed device to reduce the risk of infection from a bacteremia (secondary prophylaxis). Although it is common to prescribe secondary prophylaxis for many dental conditions, there is a general lack of scientific evidence of its effectiveness and accumulating evidence suggests that such prescriptions may be unnecessary. In the past, antibiotic prophylaxis has been used for conditions with no proven benefit. Risks associated with antibiotics include allergic reactions (for example, anaphylaxis), development of antibiotic-resistant bacteria, development of superinfections, pseudomembranous colitis, cross-reactions with other drugs, and death. The costs involved with the use of antibiotics can be significant as well. This article reviews the current status of secondary antibiotic prophylaxis use in dentistry.