This review covers four areas: the use of prophylactic antibiotics in orthopedic surgery not involving prosthetic devices; the use of prophylactic antibiotics in prosthetic joint implantation; the use of antibiotic-containing cement in prosthetic joint surgery; and the use of prophylactic antibiotics for dental procedures in individuals with implanted prosthetic joints. The major conclusions are as follows: (1) Prophylactic antimicrobial agents lower the rate of wound infection following surgery for closed hip fractures. (2) Antimicrobial prophylaxis reduces the frequency of deep wound infection following total joint replacement; operating rooms with ultraclean air have a similar effect. (3) Antibiotic-impregnated cement is as effective as systemic antibiotics in preventing early infection following total joint replacement. (4) For routine dental work in most patients with total joint replacement, there is insufficient evidence to support antibiotic prophylaxis; for such individuals with periodontal disease or potential dental infection, antimicrobial prophylaxis seems indicated.