Infection is the principal and most devastating complication of total joint replacement, resulting in long periods of hospitalization, staggering costs, loss of the implant, disastrous physical impairment, and even death. Staphylococcus aureus and Staphylococcus epidermidis account for more than 50% of late infections. Animal studies have shown that joint implants are at a high risk of becoming infected via a metastatic hematogenous route during transient bacteremias. Because cephalosporins have been established as the perioperative and intraoperative agents of choice to prevent infections related to total joint replacement, oral cephalosporins are the drugs of choice to minimize the potential for the metastatic infection of prosthetic joints associated with transient dental bacteremias. Clindamycin is preferred for patients who are allergic to the cephalosporins or who may have a cross-allergy between penicillin and the cephalosporins.